MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Investigational New Drugs' source. Wed, 08 Feb 2012 14:04:17 +0100 http://www.medworm.com/index.php?rid=5667362&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F617x7831x433t755%2F Conclusion The triple regimen of GPT is effective for APC. Treatment-related mortalities factored early closure of this GPT protocol. Considering effect and toxicity, this triple regimen seems to offer few benefits to the patients compared with gemcitabine-based doublets. (ClinicalTrials.gov number, NCT00922896). Content Type Journal ArticleCategory PHASE II STUDIESPages 1-6DOI 10.1007/s10637-012-9792-zAuthors In Gyu Hwang, Department of Internal Medicine, Chung-Ang University College of Medicine, 224 Heukseok-dong, Dongjak-gu, Seoul 156-755, Republic of KoreaJoung-Soon Jang, Department of Internal Medicine, Chung-Ang University College of Medicine, 224 Heukseok-dong, Dongjak-gu, Seoul 156-755, Republic of KoreaSung Yong Oh, Department of Medicine, Dong-A University College of Med... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5667362 Thu, 02 Feb 2012 18:12:11 +0100 5667362 http://www.medworm.com/index.php?rid=5659924&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F83q2577qt61px459%2F Summary  L-Glutamate (Glu) plays a crucial role in the growth of malignant gliomas. We have established the feasibility of accelerating a naturally occurring brain to-blood Glu efflux by decreasing blood Glu levels with intravenous oxaloacetate, the respective Glu co-substrate of the blood resident enzyme humane glutamate–oxaloacetate transaminase (hGOT). We wished to demonstrate that blood Glu scavenging provides neuroprotection in the case of glioma. We now describe the neuroprotective effects of blood Glu scavenging in a fatal condition such as brain-implanted C6 glioma in rats and brain-implanted human U87 MG glioma in nude mice. Rat (C-6) or human (U87) glioma cells were grafted stereotactically in the brain of rats or mice. After development of tumors, the animals w... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5659924 Wed, 01 Feb 2012 17:10:49 +0100 5659924 http://www.medworm.com/index.php?rid=5648112&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq13p173326467433%2F In conclusion the neurotransmitter serotonin could be successfully used to target imaging agents into human glioblastoma cells. This makes it of interest for future glioblastoma imaging methods. Content Type Journal ArticleCategory PRECLINICAL STUDIESPages 1-7DOI 10.1007/s10637-011-9781-7Authors Alexander Sturzu, Department of Neuroradiology, University of Tübingen, Hoppe-Seyler-Str. 3, 72076 Tübingen, GermanySumbla Sheikh, Peptide Synthesis Laboratory, Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, GermanyUwe Klose, Department of Neuroradiology, University of Tübingen, Hoppe-Seyler-Str. 3, 72076 Tübingen, GermanyHartmut Echner, Peptide Synthesis Laboratory, Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, GermanyHubert Ka... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5648112 Fri, 27 Jan 2012 17:54:52 +0100 5648112 http://www.medworm.com/index.php?rid=5638601&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff70186131598vrk8%2F Conclusions Sorafenib showed antitumor activity in this population of imatinib and sunitinib pretreated GIST. With sorafenib, about one third of patients can maintain disease control for more than 24 weeks. Content Type Journal ArticleCategory PHASE II STUDIESPages 1-7DOI 10.1007/s10637-012-9795-9Authors S. H. Park, Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University Samsung Medical Center, Seoul, South KoreaM. H. Ryu, Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South KoreaB. Y. Ryoo, Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South KoreaS. A. Im, Department of Internal Medicine, Seoul National University Hospital, Soeul, South KoreaH. C. Kwon, Depart... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5638601 Tue, 24 Jan 2012 07:54:04 +0100 5638601 http://www.medworm.com/index.php?rid=5638600&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy80t3276t636172l%2F Abstract  ATP-competitive mammalian target of rapamycin (mTOR) inhibitors are in early phase clinical trials. These novel targeted agents, including PP242, are mechanistically distinct from the allosteric, partial mTOR inhibitor, rapamycin. The goal of this study was to evaluate how PP242 best combines with standard chemotherapies for colorectal cancer (CRC), and which subsets of patients are most likely to benefit. The combination index for PP242 plus 5-fluorouracil, oxaliplatin, or irinotecan was determined in CRC cell lines with different mutational backgrounds. In KRAS mutant CRC cell lines, sensitivity to PP242 increases with co-mutation of PIK3CA. Mutation of p53 predicts resistance to chemotherapy, but not PP242. Efficacy of PP242 was comparable to that of standard c... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5638600 Tue, 24 Jan 2012 07:54:04 +0100 5638600 http://www.medworm.com/index.php?rid=5620269&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy8331722882m7202%2F We report that SQA induced apoptosis while a polyhalogenated monoterpene RU015 induced necrosis in metastatic breast cancer cells in vitro. Furthermore, we demonstrated that apoptosis induction by SQA occurs via caspase-3, -6, -8, -9 and -13 and was associated with down-regulation of Bcl-2. In addition, cell cycle analyses revealed that the compound causes G1 arrest in MDA-MB-231 cells. Content Type Journal ArticleCategory PRECLINICAL STUDIESPages 1-14DOI 10.1007/s10637-011-9788-0Authors Jo-Anne de la Mare, The Biomedical Biotechnology Research Unit (BioBRU), Department of Biochemistry, Microbiology and Biotechnology, Rhodes University, P. O. Box 94, Grahamstown, 6140 South AfricaJessica C. Lawson, The Biomedical Biotechnology Research Unit (BioBRU), Department of Biochemistry, Mi... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5620269 Tue, 17 Jan 2012 07:07:22 +0100 5620269 http://www.medworm.com/index.php?rid=5620270&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff4750q53mkw73173%2F Conclusions Dacomitinib 45 mg QD was defined as the RP2D and demonstrated preliminary activity in Japanese patients with advanced solid tumors. Content Type Journal ArticleCategory PHASE I STUDIESPages 1-12DOI 10.1007/s10637-011-9789-zAuthors Toshiaki Takahashi, Shizuoka Cancer Center, Shizuoka, JapanNarikazu Boku, Shizuoka Cancer Center, Shizuoka, JapanHaruyasu Murakami, Shizuoka Cancer Center, Shizuoka, JapanTateaki Naito, Shizuoka Cancer Center, Shizuoka, JapanAsuka Tsuya, Shizuoka Cancer Center, Shizuoka, JapanYukiko Nakamura, Shizuoka Cancer Center, Shizuoka, JapanAkira Ono, Shizuoka Cancer Center, Shizuoka, JapanNozomu Machida, Shizuoka Cancer Center, Shizuoka, JapanKentaro Yamazaki, Shizuoka Cancer Center, Shizuoka, JapanJunichiro Watanabe, Shizuoka Cancer Center, Shizu... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5620270 Tue, 17 Jan 2012 07:07:21 +0100 5620270 http://www.medworm.com/index.php?rid=5597947&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6nj2t46538l7t046%2F Summary  The potential of EHT 6706, a novel tubulin-binding agent, was investigated in combination with ionizing radiation (IR) and with conventional cytotoxic chemotherapy agents. Cell proliferation, cell cycle, apoptosis and clonogenic assays were performed in five human cancer cell lines: H460 (non small cell lung carcinoma, NSCLC), HCT116 and HCT116 p53-/- (colorectal cancer), MDA-MB-231 (breast cancer), and MiaPaca2 cells (pancreatic cancer). The drug inhibited cell proliferation in all cell lines. This effect was associated with G2/M arrest and activation of apoptosis in a dose-dependent manner. The drug was then tested in combination with chemotherapy and IR in vitro. Effects on proliferation and clonogenic survival were analyzed. EHT 6706 treatment inhibited clonogen... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5597947 Fri, 13 Jan 2012 16:57:57 +0100 5597947 http://www.medworm.com/index.php?rid=5597948&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm66nn27575057365%2F Summary  The basal SOCS1 mRNA levels were significantly lower in p53mutated BJAB and MAVER leukemic cell lines with respect to p53wild-type SKW6.4 and JVM-2 leukemic cell lines, p53wild-type primary B chronic lymphocytic leukemia (B-CLL) cells and primary normal peripheral blood mononuclear cells (PBMC). Moreover, the MDM2 small molecule inhibitor Nutlin-3 significantly increased the levels of SOCS1 mRNA in both primary p53wild-type B-CLL cells as well as in p53wild-type B leukemic cell lines, but not in p53mutated B leukemic cell lines nor in primary PBMC. Of note, a significant inverse correlation was observed between SOCS1 mRNA and miR-155 levels in Nutlin-3-treated primary B-CLL cells and PBMC, suggesting that the miRNA-155/SOCS1 axis represents a potentially important the... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5597948 Thu, 12 Jan 2012 06:43:03 +0100 5597948 http://www.medworm.com/index.php?rid=5582053&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F180001x5w531035u%2F Conclusion The adverse event profile associated with ipilimumab was primarily immune-related. This is the first case in which such a severe event has been reported. Content Type Journal ArticleCategory SHORT REPORTPages 1-4DOI 10.1007/s10637-011-9787-1Authors Flavie Bompaire, Service de neurologie, Hôpital d’instruction des armées du Val de Grâce, Service de santé des Armées, Paris, FranceChristine Mateus, Service de dermatologie, département d’oncologie médicale, Institut Gustave Roussy, Villejuif, FranceHervé Taillia, Service de neurologie, Hôpital d’instruction des armées du Val de Grâce, Service de santé des Armées, Paris, FranceThierry De Greslan, Service de neurologie, Hôpital d’instruction des armées du Val de Grâce, Service de santé des Armées, Par... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5582053 Tue, 10 Jan 2012 06:41:50 +0100 5582053 http://www.medworm.com/index.php?rid=5582054&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F176g3v2027876640%2F Summary  Systemic chemotherapy using two-drug platinum-based regimens for the treatment of advanced stage non-small cell lung cancer (NSCLC) has largely reached a plateau of effectiveness. Accordingly, efforts to improve survival and quality of life outcomes have more recently focused on the use of molecularly targeted agents, either alone or in combination with standard of care therapies such as taxanes. The molecular chaperone heat shock protein 90 (Hsp90) represents an attractive candidate for therapeutic intervention, as its inhibition results in the simultaneous blockade of multiple oncogenic signaling cascades. Ganetespib is a non-ansamycin inhibitor of Hsp90 currently under clinical evaluation in a number of human malignancies, including NSCLC. Here we show that gane... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5582054 Mon, 09 Jan 2012 06:32:51 +0100 5582054 http://www.medworm.com/index.php?rid=5582055&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fhl7078t1m0689864%2F In conclusion, 5F is effective against HCC with minimal side effects. It induces apoptosis in HCC cells via inhibiting NF-kB, leading to the decrease of Bcl-2 but the increase of Bax and Bak. Content Type Journal ArticleCategory PRECLINICAL STUDIESPages 1-9DOI 10.1007/s10637-011-9791-5Authors George G. Chen, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong KongJackie Leung, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong KongNian Ci Liang, Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, Guangdong, ChinaLi Li, Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, Guangdong, Chin... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5582055 Fri, 06 Jan 2012 16:48:06 +0100 5582055 http://www.medworm.com/index.php?rid=5572292&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv44271787rq00u18%2F Conclusion Dose level VIII (200 mg/m2) was considered the MTD, and dose level IX (160 mg/m2) was defined as the RD. Limited antitumor activity was observed. Content Type Journal ArticleCategory PHASE I STUDIESPages 1-9DOI 10.1007/s10637-011-9772-8Authors C. Massard, Departement de Médecine, Institut Gustave Roussy, University Paris South XI, SITEP, 39, rue Camille Desmoulins, 94805 Villejuif, FranceR. Salazar, Institut Català d’Oncologia, Barcelona, SpainJ. P. Armand, Departement de Médecine, Institut Gustave Roussy, University Paris South XI, SITEP, 39, rue Camille Desmoulins, 94805 Villejuif, FranceM. Majem, Institut Català d’Oncologia, Barcelona, SpainE. Deutsch, Departement de Médecine, Institut Gustave Roussy, University Paris South XI, SITEP, 39, rue Camille... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5572292 Wed, 04 Jan 2012 06:58:28 +0100 5572292 http://www.medworm.com/index.php?rid=5560358&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F00743x955004406r%2F Content Type Journal ArticleCategory ErratumPages 1-1DOI 10.1007/s10637-011-9783-5Authors Antonin Levy, SITEP (Service des Innovations Therapeutiques Precoces), Department of Medicine, Institut Gustave Roussy, Paris XI University, 114 rue Edouard Vaillant, 94805 Villejuif, FranceLaurence Albiges-Sauvin, SITEP (Service des Innovations Therapeutiques Precoces), Department of Medicine, Institut Gustave Roussy, Paris XI University, 114 rue Edouard Vaillant, 94805 Villejuif, FranceChristophe Massard, SITEP (Service des Innovations Therapeutiques Precoces), Department of Medicine, Institut Gustave Roussy, Paris XI University, 114 rue Edouard Vaillant, 94805 Villejuif, FranceHassan Izzedine, Department of Nephrology, AP-HP, Hôpital Pitié Salpetrière, Paris, FranceStéphane Ederhy, SITEP (S... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5560358 Mon, 02 Jan 2012 16:54:32 +0100 5560358 http://www.medworm.com/index.php?rid=5560357&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg705467780405656%2F Content Type Journal ArticleCategory ErratumPages 1-1DOI 10.1007/s10637-011-9780-8Authors Jason Konner, Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USARachel N. Grisham, Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USAJae Park, Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USAOwen A. O’Connor, New York University Cancer Institute, New York, NY, USAGillian Cropp, Nereus Pharmaceuticals, Inc, San Diego, CA, USARobert Johnson, Aeolian Biomed, Lafayette, CA, USAAlison L. Hannah, Nereus Pharmaceuticals, Inc, ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5560357 Mon, 02 Jan 2012 16:54:32 +0100 5560357 http://www.medworm.com/index.php?rid=5552456&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx052407v50327722%2F Summary  The epidermal growth factor receptor (EGFR) pathway is aberrantly activated in tumors and plays a key role in promoting tumor growth. Small molecule inhibitors which bind reversibly to EGFR have demonstrated limited clinical activity. Thus, there is a continued need to develop novel EGFR inhibitors with improved anti-tumor activity. Bay846 is a newly developed small molecule inhibitor that binds irreversibly to the tyrosine kinase domains of EGFR and Her2. The in vitro and in vivo efficacy of Bay846 was tested using a panel of nine human malignant brain tumor (glioma) models. Lapatinib, a reversible inhibitor of EGFR and Her2, was included for comparison. Six glioma cell lines were sensitive to Bay846 treatment. Bay846 strongly suppressed tumor cell growth in vitro ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5552456 Wed, 28 Dec 2011 06:53:28 +0100 5552456 http://www.medworm.com/index.php?rid=5544710&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv61rm575h5085871%2F In this study, we evaluated the efficacy of PF00299804, an irreversible pan-HER inhibitor, in eight BTC cell lines alone or combined with gemcitabine. PF00299804 potently inhibited the growth of two cell lines (SNU308 and SNU478) out of the eight BTC cell lines as a single agent. PF00299804 blocked HER family and downstream signaling pathways, inducing G1 arrest or apoptosis. Moreover, PF00299804 exerted synergistic effects with gemcitabine in seven of the eight BTC cell lines, possibly through the regulation of the genes involved in the response to gemcitabine, such as TS (thymidylate synthase), RRM1 (ribonucleotide reductase), and MAGEH1, which is negatively correlated with gemcitabine sensitivity. Our results support the need for further study of PF00299804 alone or combined with ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5544710 Sat, 24 Dec 2011 16:42:05 +0100 5544710 http://www.medworm.com/index.php?rid=5538208&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh716m2q21187132h%2F Summary  As an alternative to directly targeting of necrotic tissue using hypericin, we synthesized a conjugate of hypericin to biotin for use in a pretargeting approach. With this conjugate, we explored the possibility of a two-step pretargeting strategy using 123I-labeled avidin as effector molecule directed against necrotic RIF-1 tumors. Hypericin was conjugated to biotin-ethylenediamine in a straightforward coupling method using n-hydroxysuccinimide and dicyclohexylcarbodiimide. The necrosis avidity of the conjugate was first confirmed in necrotic liver tissue by means of fluorescence microscopy. Using autoradiography imaging and whole body-biodistribution, the accumulation of 123I-avidin in necrotic tumor tissue was evaluated 24 h after administration and 48 h... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5538208 Tue, 20 Dec 2011 16:47:36 +0100 5538208 http://www.medworm.com/index.php?rid=5538209&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg8n11648113h547n%2F Conclusions The results suggest that SM-11355 in iodized oil has similar efficacy to Zinostatin stimalamer and that repeated dosing of SM-11355 is possible without hepatic vascular injury in cases of relapse. Content Type Journal ArticleCategory PHASE II STUDIESPages 1-11DOI 10.1007/s10637-011-9776-4Authors Takuji Okusaka, Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanHiroshi Kasugai, Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, JapanHiroshi Ishii, Hepatobiliary and Pancreatic Section, Gastroenterological Division, Cancer Institute Hospital, Tokyo, JapanMasatoshi Kudo, Department of Gastroenterology and Hepatology, Kinki University, Osaka, ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5538209 Tue, 20 Dec 2011 16:47:34 +0100 5538209 http://www.medworm.com/index.php?rid=5515593&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft714072670564m5q%2F This study provides new data on FAK regulation by a natural product (TQ) which could be of a great value for the development of novel therapies in glioblastoma. Content Type Journal ArticleCategory PRECLINICAL STUDIESPages 1-11DOI 10.1007/s10637-011-9777-3Authors Kaouther Kolli-Bouhafs, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, CNRS UMR 7213, 74 route du Rhin, B.P. 60024, 67401 Illkirch, FranceAbdelaziz Boukhari, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, CNRS UMR 7213, 74 route du Rhin, B.P. 60024, 67401 Illkirch, FranceAbdurazzag Abusnina, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, CNRS UMR 7213, 74 route du Rhin, B.P. ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5515593 Wed, 14 Dec 2011 16:40:26 +0100 5515593 http://www.medworm.com/index.php?rid=5495001&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2gt77q9v3130737q%2F This study aimed to evaluate the efficacy and safety of this regimen in first-line mCRC patients. Eligible patients (age ≥20 years) had previously untreated mCRC; Eastern Cooperative Oncology Group performance status of 0–2; and adequate hematologic, hepatic, and renal function. The modified FOLFOX6 regimen and bevacizumab (5 mg/kg) was administered intravenously every 2 weeks. After 8 cycles, patients received maintenance therapy with simplified LV5FU2 and bevacizumab until completion of 8 cycles or disease progression. After maintenance therapy, patients received another 8 cycles of modified FOLFOX6 with bevacizumab until completion of 8 cycles or disease progression. We recruited 50 patients between August 2007 and January 2009. The overall response rate was 48%... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5495001 Fri, 09 Dec 2011 17:07:40 +0100 5495001 http://www.medworm.com/index.php?rid=5495002&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc7k7r7028khm4801%2F Conclusion A dosage of 10 mg everolimus daily with TMZ 150 mg/m2/day for five consecutive days every 28 days in patients is the recommended dose for this regimen. Everolimus clearance is increased by EIAEDs, and patients receiving EIAEDs should be switched to NEIAEDs before starting this regimen. Content Type Journal ArticleCategory PHASE I STUDIESPages 1-8DOI 10.1007/s10637-011-9775-5Authors Warren P. Mason, University Health Network-Princess Margaret Hospital, 610 University Avenue, Suite 18-717, Toronto, ON M5G 2M9, CanadaMary MacNeil, QEII Health Sciences Centre, Halifax, CanadaPetr Kavan, Department of Oncology, McGill University, Montréal, CanadaJacob Easaw, Tom Baker Cancer Centre, Calgary, CanadaDavid Macdonald, London Regional Cancer Centre, London, CanadaB... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5495002 Thu, 08 Dec 2011 18:11:28 +0100 5495002 http://www.medworm.com/index.php?rid=5495004&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3286743130254383%2F Conclusion The RP2D of PHA-848125AC was 150 mg/day on both schedules. Based on the responses noted in thymic carcinoma, a phase II study for patients with that disease is currently enrolling. Content Type Journal ArticleCategory PHASE I STUDIESPages 1-10DOI 10.1007/s10637-011-9774-6Authors Glen J. Weiss, Virginia G. Piper Cancer Center at Scottsdale Healthcare (VGPCC), 10510 N 92nd St, Ste 200, Scottsdale, AZ 85258, USAManuel Hidalgo, Johns Hopkins, Baltimore, MD, USAMitesh J. Borad, Virginia G. Piper Cancer Center at Scottsdale Healthcare (VGPCC), 10510 N 92nd St, Ste 200, Scottsdale, AZ 85258, USADaniel Laheru, Johns Hopkins, Baltimore, MD, USARaoul Tibes, Virginia G. Piper Cancer Center at Scottsdale Healthcare (VGPCC), 10510 N 92nd St, Ste 200, Scottsdale, AZ 85258, USARam... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5495004 Thu, 08 Dec 2011 18:11:27 +0100 5495004 http://www.medworm.com/index.php?rid=5495003&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fbl338x3703265563%2F Content Type Journal ArticleCategory ErratumPages 1-2DOI 10.1007/s10637-011-9771-9Authors Masashi Niwakawa, Division of Urology, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi, Shizuoka, 411-8777 JapanKatsuyoshi Hashine, Department of Urology, National Hospital Organization, Shikoku Cancer Center, Ehime, JapanRaizo Yamaguchi, Division of Urology, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi, Shizuoka, 411-8777 JapanHirofumi Fujii, Division of Clinical Oncology, Jichi Medical University, Tochigi, JapanYasuo Hamamoto, Department of Medical Oncology, Tochigi Cancer Center Hospital, Tochigi, JapanKoichi Fukino, Bayer Yakuhin, Ltd., Osaka, JapanTakahiko Tanigawa, Bayer Yakuhin, Ltd., Osaka, JapanYoshiteru Sumiyoshi, Department of Urology, National Hospital ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5495003 Thu, 08 Dec 2011 18:11:27 +0100 5495003 http://www.medworm.com/index.php?rid=5476730&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F79g2636361384051%2F Conclusions Our study demonstrated clinically favorable safety, tolerability, and efficacy of sagopilone, which will help define the treatment of advanced tumors in more extensive clinical trials. Content Type Journal ArticleCategory PHASE I STUDIESPages 1-7DOI 10.1007/s10637-011-9773-7Authors Kazuhiro Araki, Department of Clinical Oncology, Saitama Medical University, Saitama, JapanKoichi Kitagawa, Oncology/Hematology, National Cancer Center Hospital East, Chiba, JapanHirofumi Mukai, Oncology/Hematology, National Cancer Center Hospital East, Chiba, JapanToru Mukohara, Oncology/Hematology, National Cancer Center Hospital East, Chiba, JapanKeiji Kodama, Department of Clinical Oncology, Saitama Medical University, Saitama, JapanYuichi Ando, Department of Clinical Oncology, Saitama Me... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5476730 Sat, 03 Dec 2011 06:49:04 +0100 5476730 http://www.medworm.com/index.php?rid=5469103&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0231n058537q0847%2F Summary  The poly-(ADP-ribose) polymerase (PARP) inhibitor, MK-4827, is a novel potent, orally bioavailable PARP-1 and PARP-2 inhibitor currently in phase I clinical trials for cancer treatment. No preclinical data currently exist on the combination of MK-4827 with radiotherapy. The current study examined combined treatment efficacy of MK-4827 and fractionated radiotherapy using a variety of human tumor xenografts of differing p53 status: Calu-6 (p53 null), A549 (p53 wild-type [wt]) and H-460 (p53 wt) lung cancers and triple negative MDA-MB-231 human breast carcinoma. To mimic clinical application of radiotherapy, fractionated radiation (2 Gy per fraction) schedules given once or twice daily for 1 to 2 weeks combined with MK-4827, 50 mg/kg once daily or 25&nb... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5469103 Wed, 30 Nov 2011 04:56:04 +0100 5469103 http://www.medworm.com/index.php?rid=5449868&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc1r27898n2v3331q%2F We describe the clinical course of a 72 year-old male with a cadaveric renal transplant requiring cyclosporine that presented with a metastatic GIST and was started on imatinib at the standard dose of 400 mg daily. Imatinib initiation resulted in a decline in renal function with the serum creatinine increasing from 123 μmol/L to 196 μmol/L and an elevation in whole blood cyclosporine concentrations from 79 μg/L to 139 μg/L. No other imatinib toxicities were reported. With discontinuation of imatinib, the serum creatinine returned to baseline as did the whole blood cyclosporine levels. Ultimately, decreasing both the cyclosporine and imatinib dosing was associated with stabilized renal function (serum creatinine 150–186 μmol/L) and cyclosporin... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5449868 Thu, 24 Nov 2011 17:44:54 +0100 5449868 http://www.medworm.com/index.php?rid=5441199&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fhh8t27r1272g713u%2F Summary  Breast cancer is commonly treated with anti-estrogens or aromatase inhibitors, but resistant disease eventually develops and new therapies for such resistance are of great interest. We have previously isolated several tamoxifen-resistant variant sub-lines of the MCF-7 breast cancer cell line and provided evidence that they arose from expansion of pre-existing minor populations. We have searched for therapeutic agents that exhibit selective growth inhibition of the resistant lines and here investigate 2,6-bis(pyridin-3-ylmethylene)-cyclohexanone (RL90) and 2,6-bis(pyridin-4-ylmethylene)-cyclohexanone (RL91). We found that two of the tamoxifen-resistant sub-lines (TamR3 and TamC3) unexpectedly showed increased sensitivity to RL90 and RL91. We utilized growth inhibiti... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5441199 Mon, 21 Nov 2011 17:52:34 +0100 5441199 http://www.medworm.com/index.php?rid=5422304&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl78520641rvx420k%2F In conclusion, sorafenib is highly protein bound in human plasma with a higher affinity towards albumin and limited free drug may be partly responsible for its borderline clinical activity. Content Type Journal ArticleCategory PRECLINICAL STUDIESPages 1-7DOI 10.1007/s10637-011-9767-5Authors Maria Cristina Villarroel, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Bunting-Blaustein Cancer Research Bldg, Room 1M52, 1650 Orleans Street, Baltimore, MD 21231-1000, USAKeith W. Pratz, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Bunting-Blaustein Cancer Research Bldg, Room 1M52, 1650 Orleans Street, Baltimore, MD 21231-1000, USALinping Xu, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Bunting-Blaustein Cancer Research Bldg, Room 1M52, ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5422304 Wed, 16 Nov 2011 16:46:37 +0100 5422304 http://www.medworm.com/index.php?rid=5408399&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa0n88q03578g7125%2F Conclusions Treatment of multiple tumor cell lines with marizomib and vorinostat resulted in a highly synergistic antitumor activity. The combination of full dose marizomib with vorinostat is tolerable in patients with safety findings consistent with either drug alone. Content Type Journal ArticleCategory PHASE I STUDIESPages 1-15DOI 10.1007/s10637-011-9766-6Authors Michael Millward, Sir Charles Gairdner Hospital, University of Western Australia, Perth, AustraliaTimothy Price, The Queen Elizabeth Hospital, Adelaide, AustraliaAmanda Townsend, The Queen Elizabeth Hospital, Adelaide, AustraliaChristopher Sweeney, Royal Adelaide Hospital, Adelaide, AustraliaAndrew Spencer, The Alfred Hospital, Melbourne, AustraliaShawgi Sukumaran, The Queen Elizabeth Hospital, Adelaide, AustraliaAngie... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5408399 Fri, 11 Nov 2011 12:50:14 +0100 5408399 http://www.medworm.com/index.php?rid=5408400&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk46n886138115231%2F Conclusion KOS-862 was well tolerated with manageable toxicity, favorable PK profile, and the suggestion of clinical activity. The maximum tolerated dose was determined to be 100 mg/m2 weekly 3-on/1-off. MTBF can be demonstrated in PBMCs of patients exposed to KOS-862. Content Type Journal ArticleCategory PHASE I STUDIESPages 1-9DOI 10.1007/s10637-011-9765-7Authors Jason Konner, Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USARachel N. Grisham, Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USAJae Park, Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan-Kettering Can... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5408400 Wed, 09 Nov 2011 17:56:19 +0100 5408400 http://www.medworm.com/index.php?rid=5408401&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe165352143218110%2F Conclusions We have decided to publish the preliminary results because anti-tumor activity of nilotinib was promising in KIT mutated patients. Although our results are preliminary, nilotinib had very favorable toxicity profile with durable response in metastatic melanoma patients with KIT mutations. The anti-tumor activity of nilotinib in melanoma patients with KIT amplification is yet to be determined in future studies. Currently, phase II nilotinib trial is ongoing in Korea as multi-center study. Content Type Journal ArticleCategory PHASE II STUDIESPages 1-7DOI 10.1007/s10637-011-9763-9Authors Jin Hyun Cho, Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710 KoreaKy... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5408401 Wed, 09 Nov 2011 07:00:18 +0100 5408401 http://www.medworm.com/index.php?rid=5387187&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr4575385gn853722%2F Summary  Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Treatment options, especially in advanced tumor stages, are still limited. Inhibition of signaling cascades involved in the pathogenesis of HCC - such as NF-ĸB - offer a promising therapeutic approach. Aim of this study was to examine anti-neoplastic effects of (+)-episesamin which has been isolated from an anti-fibrotic extract of Lindera obtusiloba on human HCC cells with particular interest in activation of NF-κB. The human HCC cell lines HepG2, Huh-7 and SK-Hep1 were treated with (+)-episesamin. Beside measurement of proliferation, invasion and apoptosis, effects of (+)-episesamin on NF-κB-activity, VEGF secretion and enzymatic MMP-9 activity were determined. Anti-inflammatory ef... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5387187 Wed, 02 Nov 2011 16:55:47 +0100 5387187 http://www.medworm.com/index.php?rid=5360536&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh123595r2g775535%2F Conclusions In patients with progressive disease in whom exposure markedly decreased from baseline, sorafenib dose escalation could be considered, aiming to restore an adequate drug exposure and possibly anti-tumor activity. Content Type Journal ArticleCategory SHORT REPORTPages 1-4DOI 10.1007/s10637-011-9764-8Authors Jennifer Arrondeau, CERIA (Centre for Research on Angiogenesis Inhibitors), Department of Medical Oncology, Cochin Teaching Hospital, AP-HP, Université Paris Descartes, 27, rue du faubourg Saint Jacques, F75014 Paris, FranceOlivier Mir, CERIA (Centre for Research on Angiogenesis Inhibitors), Department of Medical Oncology, Cochin Teaching Hospital, AP-HP, Université Paris Descartes, 27, rue du faubourg Saint Jacques, F75014 Paris, FrancePascaline Boudou-Rouquette, C... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5360536 Fri, 28 Oct 2011 17:12:56 +0100 5360536 http://www.medworm.com/index.php?rid=5347718&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1666531052244424%2F Conclusions Intra-patient dose escalation and/or re-escalation of sorafenib were not feasible in pretreated solid tumor patients. Sorafenib dose escalation remains an investigational approach. Content Type Journal ArticleCategory PHASE II STUDIESPages 1-7DOI 10.1007/s10637-011-9761-yAuthors Thomas J. Semrad, Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Cancer Center, 4501 X Street, Suite 3016, Sacramento, CA 95817, USACourtney Eddings, Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Cancer Center, 4501 X Street, Suite 3016, Sacramento, CA 95817, USAChong-Xian Pan, Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Cancer Center, 4501 X S... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5347718 Thu, 20 Oct 2011 15:53:24 +0100 5347718 http://www.medworm.com/index.php?rid=5336064&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6q57350l56505241%2F Conclusion Genexol-PM was generally well tolerated and demonstrated sufficient antitumor activity to warrant further development when used as second-line chemotherapy after gemcitabine-cisplatin failure in patients with urothelial carcinoma (NCT01426126). Content Type Journal ArticleCategory PHASE II STUDIESPages 1-7DOI 10.1007/s10637-011-9757-7Authors Jae-Lyun Lee, Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 138-736 KoreaJin-Hee Ahn, Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 138-736 KoreaSe Hoon Park, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaHo Young Lim, Depart... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5336064 Wed, 19 Oct 2011 15:52:46 +0100 5336064 http://www.medworm.com/index.php?rid=5336065&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe3vuk3r363gn4348%2F Summary  Sorafenib is an oral tyrosine kinase inhibitor approved for the treatment of advanced renal cell carcinoma and hepatocellular carcinoma. By using a population approach, this study aimed to characterise its pharmacokinetics. Plasma concentration-time data (n = 372) from 71 patients under sorafenib were analysed using nonlinear mixed-effect modelling to estimate population pharmacokinetic parameters, as well as relationships between these parameters and different covariates (demographic, biological). Simulations were done to compare different daily dosing regimens in a context of dose-escalation. A 1-compartment model with saturated absorption, first-order intestinal loss and elimination best described the pharmacokinetics of sorafenib. Absolute bioavailability s... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5336065 Mon, 17 Oct 2011 16:01:15 +0100 5336065 http://www.medworm.com/index.php?rid=5336067&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd2u1873583806867%2F Summary  We conducted a phase I trial to determine the feasible dose for lapatinib, a dual HER2/EGFR tyrosine kinase inhibitor, with paclitaxel and gemcitabine as a neoadjuvant treatment in HER2 positive patients. In this phase I dose-escalation study, cohorts of 3–6 HER2-positive operable breast cancer patients received lapatinib (1,000 mg/day or 1,250 mg/day PO) with paclitaxel (80 mg/m2) and gemcitabine (1,000 or 1,200 mg/m2) on days 1 and 8 every 21 days to determine the tolerable dosages. Among 13 patients enrolled, 12 (stage III; n = 11: stage II; n = 1) completed treatment and one withdrew consent. The recommended doses were 1000-mg/day lapatinib, 80-mg/m2 paclitaxel, and 1,000-mg/m2 gemcitabine. One patient developed dose-limiting gra... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5336067 Mon, 17 Oct 2011 16:01:14 +0100 5336067 http://www.medworm.com/index.php?rid=5336066&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm61366582u0225w4%2F Summary  Cancer is one of the major causes of death for non-transmissible chronic diseases worldwide. Conventional treatments including surgery, chemotherapy and external beam radiotherapy are generally far from curative. Complementary therapies are attempted for achieving more successful treatment response. Systemic targeted radiotherapy (STR) is a radiotherapeutic modality based on systemic administration of radioactive agents for selectively delivering high doses of energy to destroy cancer cells. For this purpose, diverse tumour-target specific agents including monoclonal antibodies (MoAb), MoAb fragments and peptides have been tested and some of them have already got FDA approval for clinical use. However, MoAbs and their tailored analogues have shown non-homogeneous t... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5336066 Mon, 17 Oct 2011 16:01:14 +0100 5336066 http://www.medworm.com/index.php?rid=5324159&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk2675711656q6x21%2F In conclusion, the lipophilic derivatives elacytarabine and CP-4126 showed a nucleoside-transporter independent uptake, with long retention of the active nucleotides. These lipophilic nucleoside analogues are new chemical entities suitable for novel clinical applications. Content Type Journal ArticleCategory PRECLINICAL STUDIESPages 1-9DOI 10.1007/s10637-011-9756-8Authors Auke D. Adema, Department of Medical Oncology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, the NetherlandsKees Smid, Department of Medical Oncology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, the NetherlandsNienke Losekoot, Department of Medical Oncology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, the NetherlandsRichard J. Honeywell, Department of Medical On... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5324159 Fri, 14 Oct 2011 10:47:59 +0100 5324159 http://www.medworm.com/index.php?rid=5324160&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj1n5028793255352%2F Summary  Targeting angiogenesis is a valid anti-cancer strategy. Aflibercept is designed to sequester circulating vascular endothelial growth factor (VEGF) by preventing VEGF from binding to its receptors. This phase I study was to evaluate a new formulation of subcutaneously administered aflibercept in patients with advanced solid tumors. Here we report our experience with the toxicity, pharmacokinetic profile and efficacy of the new 100 mg/mL subcutaneous (SC) formulation of aflibercept administered at a dose of at 4 mg/kg every 2 weeks. Content Type Journal ArticleCategory PHASE I STUDIESPages 1-4DOI 10.1007/s10637-011-9753-yAuthors Andrea Wang-Gillam, Washington University School of Medicine, 660 South Euclid Ave, Campus Box 8056, St. Louis, MO 63110... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5324160 Fri, 14 Oct 2011 10:47:58 +0100 5324160 http://www.medworm.com/index.php?rid=5324161&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb6gp8454301t42w1%2F This study investigated the detailed biological mechanism of ZJU-6 in comparison with that of Erianin. Both ZJU-6 and Erianin substantially reduced cell viability and induced apoptosis in human cancer cell lines. Profound G2/M cell arrest was observed 24 h after treatment of MCF-7 cells with ZJU-6 (≥ 2.5 μM) or Erianin (≥ 0.1 μM); being consistent with mitotic collapse. 0.5 μM of Erianin or ZJU-6 failed to stabilise tubulin. Pre-G1 MCF-7 cell accumulating 24 h post treatment indicated apoptosis. Caspase-3 activity, PARP cleavage and Annexin V + ve /PI -ve populations correlate the apoptotic destiny of cells exposed to either ZJU-6 or Erianin. Furthermore ZJU-6 showed potent anti-angiogenetic property and demonstrated radical scavenging capacity. Du... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5324161 Thu, 13 Oct 2011 15:49:13 +0100 5324161 http://www.medworm.com/index.php?rid=5314699&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj8px17878035u9u5%2F Conclusions All cediranib doses were tolerated; however, in patients with advanced solid tumours, for combination with saracatinib 175 mg/day, cediranib 20 or 30 mg/day was more sustainable than 45 mg/day. Content Type Journal ArticleCategory PHASE I STUDIESPages 1-10DOI 10.1007/s10637-011-9754-xAuthors Tanja Trarbach, Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisbug-Essen Essen, Hufelandstr. 55, 45122 Essen, GermanyBeate Schultheis, Marienhospital Herne, Herne, GermanyThomas C. Gauler, Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisbug-Essen Essen, Hufelandstr. 55, 45122 Essen, GermanyVesile Schneider, Cancer Hospital SanaFontis, Freiburg, GermanyDirk Strumb... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5314699 Tue, 11 Oct 2011 15:53:00 +0100 5314699 http://www.medworm.com/index.php?rid=5314700&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2481625xw7351471%2F Summary  Standard therapy for advanced or metastatic non-small cell lung cancer (NSCLC) has primarily consisted of traditional cytotoxic chemotherapy, although use of targeted therapies has been approved in specific settings. Antiangiogenic agents represent a promising therapeutic strategy for treatment of advanced NSCLC. Bevacizumab is currently approved when given in combination with first-line platinum-based therapy in selected patients with nonsquamous NSCLC. Bevacizumab may also provide benefit in other clinical settings, as a part of a combination or maintenance strategy. Other antiangiogenic agents under development, including multi-targeted kinase inhibitors (MTKIs) and antibody-based agents, have exhibited mixed results in the NSCLC population. Published efficacy a... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5314700 Mon, 10 Oct 2011 15:01:32 +0100 5314700 http://www.medworm.com/index.php?rid=5304594&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc8105812n5702611%2F In this study, we synthesized a novel histone deacetylase (HDAC) inhibitor, MHY218, for the development of potent inhibitors of HDAC and evaluated its biological activities by monitoring the anticancer effects in Tam-resistant MCF-7 (TAMR/MCF-7) cells via in vitro and in vivo studies. MHY218 significantly inhibited the proliferation of TAMR/MCF-7 cells in a dose-dependent manner. The total HDAC enzyme activity was significantly inhibited, corresponding with inhibition of acetylated H3 and H4 expression in TAMR/MCF-7 cells. HDAC1, 4, and 6 expression levels were decreased in response to MHY218 treatment. Cell cycle analysis indicated that MHY218 induced G2/M phase cell cycle arrest. As expected, apoptotic cell death was observed in response to MHY218 treatment. Interestingly, levels o... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5304594 Fri, 07 Oct 2011 15:58:03 +0100 5304594 http://www.medworm.com/index.php?rid=5285888&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx84t7412704331x2%2F Summary  Panobinostat (LBH589) is a potent pan-histone deacetylase inhibitor. As a result of promising preclinical data, Phase I and II clinical trials of intravenous and oral panobinostat have been conducted in patients with a wide variety of hematologic and solid tumors. This is the first report of a phase I study to evaluate intravenous panobinostat given on days 1 and 8 of a 21-day cycle in patients with solid tumors. The primary objective was to characterize the safety and tolerability of panobinostat by evaluating the occurrence of dose-limiting toxicity (DLT) and determining the maximum tolerated dose (MTD) in Japanese patients with advanced solid tumors. Secondary objectives included characterizing the pharmacokinetics and assessing antitumor activity. Fourteen pati... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5285888 Sat, 01 Oct 2011 06:44:50 +0100 5285888 http://www.medworm.com/index.php?rid=5237992&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fdx7478301q2123u7%2F Summary  Antiproliferative factor (APF) is a potent frizzled protein 8-related sialoglycopeptide inhibitor of bladder epithelial cell proliferation that mediates its activity by binding to cytoskeletal associated protein 4 in the cell membrane. Synthetic asialylated APF (as-APF) (Galβ1-3GalNAcα-O-TVPAAVVVA) was previously shown to inhibit both normal bladder epithelial as well as T24 bladder carcinoma cell proliferation and heparin-binding epidermal growth factor-like growth factor (HB-EGF) production at low nanomolar concentrations, and an L-pipecolic acid derivative (Galβ1-3GalNAcα-O-TV-pipecolic acid-AAVVVA) was also shown to inhibit normal bladder epithelial cell proliferation. To better determine their spectrum of activity, we measured the effects of these APF deriv... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5237992 Mon, 19 Sep 2011 13:42:50 +0100 5237992 http://www.medworm.com/index.php?rid=5237991&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm374w5166062k281%2F Conclusions The combination of trabectedin and capecitabine is generally well tolerated, without pharmacokinetic interactions, and shows some activity in patients with advanced cancers. Content Type Journal ArticleCategory PHASE I STUDIESPages 1-8DOI 10.1007/s10637-011-9747-9Authors Lia Gore, University of Colorado Cancer Center, 13123 East 16th Ave, Box B115 TCH, Aurora, CO 80045, USAE. Rivera, M. D. Anderson Cancer Center, Houston, TX, USAM. Basche, University of Colorado Cancer Center, 13123 East 16th Ave, Box B115 TCH, Aurora, CO 80045, USAS. L. Moulder-Thompson, M. D. Anderson Cancer Center, Houston, TX, USAJ. Li, Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Raritan, NJ, USAS. Eppers, University of Colorado Cancer Center, 13123 East 16th Ave, Box B115 TCH, ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5237991 Mon, 19 Sep 2011 13:42:50 +0100 5237991 http://www.medworm.com/index.php?rid=5237990&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn285r0h08u34h122%2F Summary  Chronic inflammation is associated with 25% of all cancers. In the inflammation-cancer axis, prostaglandin E2 (PGE2) is one of the major players. PGE2 synthases (PGES) are the enzymes downstream of the cyclooxygenases (COXs) in the PGE2 biosynthesis pathway. Microsomal prostaglandin E2 synthase 1 (mPGES-1) is inducible by pro-inflammatory stimuli and constitutively expressed in a variety of cancers. The potential role for this enzyme in tumorigenesis has been reported and mPGES-1 represents a novel therapeutic target for cancers. In order to identify novel small molecule inhibitors of mPGES-1, we screened the ChemBridge library and identified 13 compounds as potential hits. These compounds were tested for their ability to bind directly to the enzyme using surface plas... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5237990 Mon, 19 Sep 2011 13:42:50 +0100 5237990 http://www.medworm.com/index.php?rid=5225968&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh27114ghk2635230%2F Conclusions PCR and FCR have significant activity in CLL and can be given safely in the community setting despite significant toxicity. ORRs were lower than expected; the CR rate was higher (NS) with FCR. This trial did not demonstrate a lower infection rate with PCR. Content Type Journal ArticleCategory PHASE III STUDIESPages 1-9DOI 10.1007/s10637-011-9737-yAuthors Craig Reynolds, US Oncology Research, LLC., The Woodlands, TX, USANicholas Di Bella, US Oncology Research, LLC., The Woodlands, TX, USARoger M. Lyons, US Oncology Research, LLC., The Woodlands, TX, USAWilliam Hyman, US Oncology Research, LLC., The Woodlands, TX, USADonald A. Richards, US Oncology Research, LLC., The Woodlands, TX, USAGerald J. Robbins, US Oncology Research, LLC., The Woodlands, TX, USAMark Vellek, US O... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5225968 Thu, 15 Sep 2011 15:49:36 +0100 5225968 http://www.medworm.com/index.php?rid=5225970&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv836v8g332t43864%2F Conclusion Compound 5 restores p53-like function to a human tumour cells lines expressing a variety of mutant p53 proteins, thus providing a basis for the design of further new drugs. Content Type Journal ArticleCategory SHORT REPORTPages 1-11DOI 10.1007/s10637-011-9744-zAuthors Hamish S. Sutherland, Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New ZealandIn Young Hwang, Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New ZealandElaine S. Marshall, Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New ZealandBrent S... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5225970 Mon, 12 Sep 2011 15:50:02 +0100 5225970 http://www.medworm.com/index.php?rid=5225969&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv15v0h03825238v3%2F Summary  Resveratrol (3, 4′, 5-trihydroxy-trans-stilbene), a natural phytoalexin found in grapes and wine, has anti-proliferative activity on human-derived cancer cells. In our study, we used a conventional condensation reaction between aldehydes and amines to provide a number of aza-resveratrol (3, 4′, 5-trihydroxy-trans- aza-stilbene) derivatives in an attempt to screen for compounds with resveratrol’s action but with increased potency. Aza-resveratrol and its hydroxylated derivative (3, 4, 4′, 5-tetrahydroxy-trans- aza-stilbene) showed a more enhanced anti-proliferative effect than resveratrol in an MCF-7 breast carcinoma cell line. To identify the cellular targets of the aza derivatives of resveratrol, we conjugated the latter aza-stilbene compound with epoxy-act... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5225969 Mon, 12 Sep 2011 15:50:02 +0100 5225969 http://www.medworm.com/index.php?rid=5209091&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk74624u184k57vr3%2F Summary  Nimotuzumab (h-R3) is a humanized anti-epidermal growth factor receptor monoclonal antibody. We conducted a phase I study to assess the safety, tolerance, maximal tolerance dose (MTD) and efficacy of h-R3 in combination with concurrent chemoradiation in patient with locally advanced esophageal carcinoma. Patients with locally advanced squamous cell carcinoma of esophagus were eligible. A total dose of 61.2 Gy was delivered by conventional fractionation. Chemotherapy was concurrently administered with irradiation every 4 weeks with PF regimen (cis-platinum of 25 mg/m2/d, d1-3; 5-Fu of 1,800 mg/m2, intravenously infusion in 72 h) for 4 cycles. h-R3 was administrated weekly during irradiation for 6 weeks. h-R3 dose escalation started with ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5209091 Thu, 08 Sep 2011 06:10:57 +0100 5209091 http://www.medworm.com/index.php?rid=5209092&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy2079j85h7808683%2F In conclusion, cluvenone, an agent with potent cytotoxicity against multi-drug resistant tumor cells, has direct targets in mitochondria thus setting precedence for drug discovery efforts against these targets in the treatment of refractory cancers. Content Type Journal ArticleCategory PRECLINICAL STUDIESPages 1-8DOI 10.1007/s10637-011-9745-yAuthors Gianni Guizzunti, Department of Cell Biology and Infection, Membrane Traffic and Pathogenesis Unit, Pasteur Institute, Paris, FranceEmmanuel A. Theodorakis, Department of Chemistry and Biochemistry, University of California, 9500 Gilman Drive, La Jolla, San Diego, CA 92093, USAAlice L. Yu, The Genomics Research Center, Academia Sinica, Taipei, TaiwanChiara Zurzolo, Department of Cell Biology and Infection, Membrane Traffic and Pathogen... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5209092 Tue, 06 Sep 2011 15:43:38 +0100 5209092 http://www.medworm.com/index.php?rid=5209093&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl0r11220g2878p14%2F We report here on an update of efficacy and safety of the SIR plus bevacizumab (SIRB) regimen as first line treatment for mCRC patients. Fifty-one eligible patients with histologically confirmed advanced or recurrent colorectal cancer received this treatment. S-1 was administered orally on days 1–14 of a 21-day cycle. Patients were assigned on the basis of body surface area (BSA) to receive one of the following oral doses twice daily: 40 mg, 50 mg, or 60 mg. Irinotecan (150 mg/m2) plus bevacizumab (7.5 mg/kg) were administered by intravenous infusion on day 1. Safety analysis identified a grade 3/4 neutropenia rate of 26%. Other grade 3/4 toxicities were diarrhea (8%), nausea (6%), vomiting (2%), and hypertension (8%). The response rate was 67% and the medi... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5209093 Mon, 05 Sep 2011 16:15:27 +0100 5209093 http://www.medworm.com/index.php?rid=5196610&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe1765137u268605m%2F Summary  Aplidin is a novel cyclic depsipeptide, currently in Phase II/III clinical trials for solid and hematologic malignancies. The aim of this study was to evaluate the effect of Aplidin in chronic lymphocytic leukemia (CLL), the most common leukemia in the adult. Although there have been considerable advances in the treatment of CLL over the last decade, drug resistance and immunosuppression limit the use of current therapy and warrant the development of novel agents. Here we report that Aplidin induced a dose- and time-dependent cytotoxicity on peripheral blood mononuclear cells (PBMC) from CLL patients. Interestingly, Aplidin effect was markedly higher on monocytes compared to T lymphocytes, NK cells or the malignant B-cell clone. Hence, we next evaluated Aplidin act... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5196610 Fri, 02 Sep 2011 05:50:36 +0100 5196610 http://www.medworm.com/index.php?rid=5196611&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm5810725qx4l2057%2F Summary  Eribulin mesylate (Halaven™, E7389) is a synthetic analog of the marine natural product halichondrin B that acts via a mechanism distinct from conventional tubulin-targeted agents. This Phase I study (clinicaltrials.gov identifier: NCT00326950) was the first to investigate eribulin mesylate in Japanese patients. The study determined the recommended dose, MTD, DLTs, safety, pharmacokinetics, and antitumor activity of eribulin administered on Days 1 and 8 of a 21-day cycle in Japanese patients with advanced solid tumors. Fifteen patients received eribulin mesylate 0.7–2.0 mg/m2 as a 2- to 10-min intravenous injection. Neutropenia was the principal DLT. DLTs were observed in two of six patients treated at 1.4 mg/m2, and in all three patients at 2.0 m... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5196611 Fri, 02 Sep 2011 05:50:34 +0100 5196611 http://www.medworm.com/index.php?rid=5184210&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3t1g072022r654w0%2F Conclusions This combination of agents is associated with tolerable toxicities at doses that induced responses. PK studies revealed no interaction between the drugs. Further investigations of this targeting strategy may be attractive in renal cell carcinoma, non-small cell lung cancer, alveolar sarcoma, and carcinoid tumor. Content Type Journal ArticleCategory PHASE I STUDIESPages 1-8DOI 10.1007/s10637-011-9742-1Authors Alan H. Bryce, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ 85255, USARavi Rao, Mayo Clinic, Rochester, MN, USAJann Sarkaria, Mayo Clinic, Rochester, MN, USAJoel M. Reid, Mayo Clinic, Rochester, MN, USAYingwei Qi, Mayo Clinic, Rochester, MN, USARui Qin, Mayo Clinic, Rochester, MN, USAC. David James, University of California, San Francisco, San Francisco, CA, USAR... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5184210 Wed, 31 Aug 2011 15:56:03 +0100 5184210 http://www.medworm.com/index.php?rid=5184212&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa424826m12w73147%2F Conclusions Dasatinib 150 mg once daily plus weekly cetuximab is recommended for phase II studies. Early-onset headache was ameliorated by starting dasatinib after cetuximab. Content Type Journal ArticleCategory PHASE I STUDIESPages 1-10DOI 10.1007/s10637-011-9732-3Authors Athanassios Argiris, Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USATrevor M. Feinstein, Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USALin Wang, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USATianbing Yang, Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USAShruti Agrawal, Brist... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5184212 Wed, 31 Aug 2011 15:56:02 +0100 5184212 http://www.medworm.com/index.php?rid=5184211&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fjj657n864m1r9038%2F In this study, the intracellular apoptosis signaling pathways of two melanoma cells lines (SK-MEL-2 and SK-MEL-28) were investigated after treatment with a new experimental antifolate substance (MR36) that targets thymidylate synthase. In both melanoma cell lines, apoptosis induction was triggered by a p53-independent mechanism. MR36-induced apoptosis was associated with a loss of both mitochondrial membrane potential and caspase-3 activation. Induction of cell cycle arrest by MR36 was associated with changes in the expression of key cell cycle regulators, such as p21 and cyclin D1, and the hypophosphorylation of pRb. In addition, Fas signaling was also analyzed. These findings suggest that, unlike classical antifolates, MR36 exerted an inhibitory effect on both the enzymatic functio... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5184211 Wed, 31 Aug 2011 15:56:02 +0100 5184211 http://www.medworm.com/index.php?rid=5184213&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr51g68022419p3n2%2F In conclusion, the present findings indicate that TQ is a novel anti-microtubule drug which targets the level of α/β tubulin proteins in cancer cells. Furthermore, they highlight the interest of developing anti-cancer therapies that target directly tubulin rather than microtubules dynamics. Content Type Journal ArticleCategory PRECLINICAL STUDIESPages 1-7DOI 10.1007/s10637-011-9734-1Authors Mahmoud Alhosin, CNRS UMR 7213 Laboratoire de Biophotonique et Pharmacologie, Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin, 67401 Illkirch, FranceAbdulkhaleg Ibrahim, CNRS UMR 7213 Laboratoire de Biophotonique et Pharmacologie, Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin, 67401 Illkirch, FranceAbdelaziz Boukhari, CNRS UMR 7213 Laboratoire de Biopho... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5184213 Wed, 31 Aug 2011 15:56:01 +0100 5184213 http://www.medworm.com/index.php?rid=5170495&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F92254h454246t88p%2F We report here that a synthetic decursin analog, decursinol phenylthiocarbamate (DPTC), has greater in vivo stability than the parent compounds. DPTC-decursinol conversion was undetectable in mice. Furthermore, in LNCaP cells, DPTC decreased prostate specific antigen (PSA) expression, down-regulated AR abundance and mRNA and inhibited AR nuclear translocation. The effect of DPTC on AR and PSA mRNA and protein abundance was also observed in VCaP cells expressing wild type AR. DPTC inhibited growth of both PCa cell lines through G1 cell cycle arrest and apoptosis, as did decursin and DA. Furthermore, i.p. administration of DPTC for 3 weeks suppressed the expression of AR target genes probasin and Nkx3.1 in mouse prostate glands. Overall, our data suggest that DPTC represents a prot... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5170495 Thu, 25 Aug 2011 15:49:34 +0100 5170495 http://www.medworm.com/index.php?rid=5161999&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F920731310wv800j2%2F Conclusion PX-12 administered at 400 mg/m2/day by 72-hour infusion appears safe and tolerable. Inhibition of thioredoxin is a strategy worth evaluation with next generation of inhibitors. Content Type Journal ArticleCategory PHASE I STUDIESPages 1-6DOI 10.1007/s10637-011-9739-9Authors Ramesh K. Ramanathan, Virginia G Piper Cancer Center/TGen, Scottsdale, AZ, USAJoe J. Stephenson, Greenville Hospital System, Institute for Translational Oncology Research, Greenville, SC, USAGlen J. Weiss, Virginia G Piper Cancer Center/TGen, Scottsdale, AZ, USALinda A. Pestano, Oncothyreon Inc, Seattle, WA, USAAnn Lowe, Oncothyreon Inc, Seattle, WA, USAAlton Hiscox, Oncothyreon Inc, Seattle, WA, USARafael A. Leos, Oncothyreon Inc, Seattle, WA, USAJulie C. Martin, Greenville Hospital System, Inst... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5161999 Tue, 23 Aug 2011 15:52:49 +0100 5161999 http://www.medworm.com/index.php?rid=5161998&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh4pg3l5u88601153%2F Conclusion Gefitinib was well tolerated but of limited efficacy in patients with recurrent or metastatic esophageal or GEJ cancer. Further study of this or similar agents will require better patient selection. Content Type Journal ArticleCategory PHASE II STUDIESPages 1-6DOI 10.1007/s10637-011-9736-zAuthors David J. Adelstein, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USACristina P. Rodriguez, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USALisa A. Rybicki, Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USADenise I. Ives, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USAThomas W. Rice, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA Journal Investigational New DrugsOnline ISSN 1573-0... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5161998 Tue, 23 Aug 2011 15:52:49 +0100 5161998 http://www.medworm.com/index.php?rid=5162000&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F384k8r14u2kvhv1h%2F In conclusion, MDMA analogues have been discovered with enhanced cytotoxic efficacy against lymphoma subtypes amongst which high-level Bcl-2—often a barrier to drug performance for this indication—fails to protect. Content Type Journal ArticleCategory PRECLINICAL STUDIESPages 1-13DOI 10.1007/s10637-011-9730-5Authors Agata M. Wasik, School of Immunity & Infection, The Medical School, Birmingham, University of Birmingham, Edgbaston, Birmingham, B15 2TT UKMichael N. Gandy, School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, Crawley, AustraliaMatthew McIldowie, School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, Crawley, AustraliaMichelle J. Holder, School of Immunity & Infection, The Medical Scho... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5162000 Thu, 18 Aug 2011 05:48:29 +0100 5162000 http://www.medworm.com/index.php?rid=5162001&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5287764j67347j54%2F Conclusions Postoperative adjuvant S-1 plus cisplatin for 18 weeks was found to be feasible for patients with stage II-IV (M0) gastric adenocarcinoma following complete surgical resection. Content Type Journal ArticleCategory PHASE II STUDIESPages 1-5DOI 10.1007/s10637-011-9729-yAuthors Byung Woog Kang, Department of Hematology/Oncology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 200 Dongduk-Ro, Jung-Gu, Daegu, Korea 700-712Jong Gwang Kim, Department of Hematology/Oncology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 200 Dongduk-Ro, Jung-Gu, Daegu, Korea 700-712Yee Soo Chae, Department of Hematology/Oncology, Kyungpook National University Hospital, Kyungpook National University School ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5162001 Tue, 16 Aug 2011 06:10:14 +0100 5162001 http://www.medworm.com/index.php?rid=5126479&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F716805674p777555%2F Conclusions The pharmacokinetics of KOS-862 were similar in this combination study to those seen in previous monotherapy studies using the same route and time of administration. We have described the MTD of this schedule. The neurotoxicity seen with this regimen should be considered prior to its administration in unselected populations. Content Type Journal ArticlePages 1-8DOI 10.1007/s10637-011-9731-4Authors J. Paul Monk, Ohio State University, Columbus, OH, USAMiguel Villalona-Calero, Ohio State University, Columbus, OH, USAJoe Larkin, Memorial Sloan-Kettering Cancer Center, New York, NY, USAGreg Otterson, Ohio State University, Columbus, OH, USADavid S. Spriggs, Memorial Sloan-Kettering Cancer Center, New York, NY, USAAlison L. Hannah, Kosan Biosciences, Hayward, CA, USAGillian... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5126479 Mon, 08 Aug 2011 19:52:18 +0100 5126479 http://www.medworm.com/index.php?rid=5126480&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6t03483311622055%2F Summary  The combination of anti-cancer drugs with nutritional factors is a potential strategy for improving the efficacy of chemotherapy, particularly for hepatocellular carcinoma because its conventional therapies are mostly ineffective. Using a highly invasive hepatoma SK-Hep-1 cell line, we investigated the possible synergistic anti-metastatic efficacy of a combination of sorafenib (SF), a multi-kinase inhibitor, and β-ionone (BI), a precursor of carotenoids. We found that SF (1 μM) in combination with BI (1 μM) synergistically inhibited cell invasion and additively inhibited cell migration, especially at 48 h of incubation. Mechanistically, the combination of SF and BI was found to decrease the protein expression of focal adhesion kinase (FAK) and Rho... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5126480 Mon, 08 Aug 2011 19:52:14 +0100 5126480 http://www.medworm.com/index.php?rid=5098015&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh31673420500n522%2F Summary  Because cancer patients may have difficulty swallowing whole tablets, crushing tablets or ingesting an oral suspension is a practical alternative. This open-label, 2-part, randomized crossover, phase I study evaluated the pharmacokinetics and tolerability of pazopanib administered as a crushed tablet or an oral suspension relative to whole tablet in patients with advanced cancer (Part 1). Patients completing Part 1 were eligible for continuous daily pazopanib 800 mg (Part 2). Administration of a single pazopanib 400 mg crushed tablet increased the area under the curve from 0 to 72 h (AUC(0–72); 46%) and maximum observed plasma concentration (Cmax; ~2-fold), and decreased time to achieve maximum plasma concentration (Tmax; ~2 h), indicating incre... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5098015 Tue, 02 Aug 2011 16:04:10 +0100 5098015 http://www.medworm.com/index.php?rid=5098016&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F91643471k7n45167%2F Summary  The purpose of this study was to evaluate the efficacy of postoperative adjuvant chemotherapy with FOLFOX regimen on the outcome after LT for HCC patients who did not meet the Milan criteria. Ninety-five consecutive HCC patients with liver cirrhosis undergoing LT were enrolled. Fifty-eight who did not meet the Milan criteria were randomized to open-label treatment with or without adjuvant chemotherapy after LT (n = 29/group). The FOLFOX chemotherapy protocol comprised 3-week cycles of oxaliplatin 100 mg/m2 on day 1, leucovorin (calcium folinate, CF) 200 mg/m2 on day 1 followed by 3-day, and 5-fluorouracil (5-FU) 2000 mg/m2 as a 48-h continuous infusion, for up to six courses in the 1st year after transplantation. Median survival was extended by 4.5... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5098016 Tue, 02 Aug 2011 06:15:17 +0100 5098016 http://www.medworm.com/index.php?rid=5098017&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq47p76170352r8k0%2F The objective of the present study was to determine the in-vitro effect of Abietyl-Isothiocyanate (ABITC), a representative of a new class of anti-cancer drugs, on endometrial cancer (EC) cell lines. ABITC at concentrations ≥1 μM displayed dose-dependent and selective cytotoxicity to EC cell lines (ECC-1, AN3CA, RL95-2) in comparison to other cancer cell lines. After treatment with ABITC, ECC-1 unlike control cells displayed hallmark features of apoptosis including chromatin condensation and nuclear fragmentation. At concentrations below the IC50, ABITC exerted anti-proliferative effects by blocking cell-cycle progression through G0/G1 and S-phase. In addition, cells attempted to counteract drug treatment by pro-survival signaling such as deactivation of JNK/SAPK and p38 MAPK... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5098017 Tue, 02 Aug 2011 06:15:16 +0100 5098017 http://www.medworm.com/index.php?rid=5098018&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8q92r44m8rt68v12%2F Conclusion Everolimus 10 mg/day continuously combined with capecitabine 1,000 mg/m2 bid for 14 days every 3 weeks is a patient-convenient, safe and tolerable oral treatment regimen. This is the first study to demonstrate feasibility of this combination at doses with proven single agent efficacy in a number of tumors. Prolonged clinical benefit was observed in an encouraging 39% of patients with advanced solid malignancies. Content Type Journal ArticlePages 1-9DOI 10.1007/s10637-011-9723-4Authors Maarten J. Deenen, Division of Clinical Pharmacology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The NetherlandsHeinz-Josef Klümpen, Department of Medical Oncology, Academic Medical Center Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5098018 Tue, 02 Aug 2011 06:15:15 +0100 5098018 http://www.medworm.com/index.php?rid=5088673&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv54964281h7u3310%2F Conclusions MKC-1 administration was associated with substantial toxicity and did not demonstrate sufficient activity in patients with advanced pancreatic cancer to justify further exploration in this patient population. Content Type Journal ArticlePages 1-7DOI 10.1007/s10637-011-9708-3Authors Jason E. Faris, Department of Medical Oncology, Massachusetts General Hospital Cancer Center, POB 221, Boston, MA 02114, USAJamie Arnott, Entremed, Inc., Durham, NC, USAHui Zheng, Biostatistics Center, Massachusetts General Hospital, Boston, MA, USADavid P. Ryan, Department of Medical Oncology, Massachusetts General Hospital Cancer Center, Yawkey 7E, Boston, MA 02114, USAThomas A. Abrams, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USALawrence S. Blaszkowsky, Dep... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5088673 Thu, 28 Jul 2011 15:54:16 +0100 5088673 http://www.medworm.com/index.php?rid=5079677&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn55m631105615310%2F Conclusions Although the gefitinib/irinotecan combination was very tolerable and induced responses, it was not sufficiently active to warrant further investigation. Initial investigational studies of this type can preclude the necessity for larger, longer, and costlier trials. Content Type Journal ArticlePages 1-11DOI 10.1007/s10637-011-9724-3Authors Wayne L. Furman, Department of Oncology, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USALisa M. McGregor, Department of Oncology, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USAM. Beth McCarville, Department of Radiological Sciences, St. Jude Children’s Research Hospital, Memphis, TN, USAMihaela Onciu, Department of Pathology, St. Jude Children’s Resea... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5079677 Wed, 27 Jul 2011 15:50:38 +0100 5079677 http://www.medworm.com/index.php?rid=5070368&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fep79380415333151%2F Content Type Journal ArticlePages 1-2DOI 10.1007/s10637-011-9713-6Authors György Bodoky, Department of Oncology, St. László Hospital, Gyáli út 5-7, 1097 Budapest, HungaryConstanta Timcheva, National Oncology Centre, Clinic of Chemotherapy, 5 Plovdivsko pole St., 1756 Sofia, BulgariaDavid Robert Spigel, Sarah Cannon Research Institute, (SCRI), 250 25th Avenue North, Suite 110, Nashville, TN 37203, USAPhillip Joseph La Stella, St. Joseph Mercy Hospital Cancer Care Center, 5301 East Huron River Drive, P.O. Box 995, Ann Arbor, MI 48106-0995, USATudor Eliade Ciuleanu, Day Hospital Department-Medical Oncology, Oncological Institute I Chiricuta, Republicii 34-36 str, Cluj-Napoca, 40015 RomaniaG. Pover, AstraZeneca, Alderley Park, UKN. C. Tebbutt, Austin Heath, Heidelberg, VIC 3084, Austr... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5070368 Mon, 25 Jul 2011 15:45:24 +0100 5070368 http://www.medworm.com/index.php?rid=5070367&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F727n56061034250n%2F This study evaluates the anti-proliferative activity of series of acridine-based catalytic inhibitors of hTopoII using four mesothelioma cell lines (H513, H2372, H2461, and H2596). The results indicate these compounds inhibit malignant cell proliferation with EC50 values ranging from 6.9 to 32 μM. Experiments are also performed that show that combination therapies may be used to increase potency. Based on the results of PARP cleavage and Guava Nexin assay, it is concluded that the primary mode of cell death is by apoptosis. The results are consistent with prior work involving pancreatic cancer and hTopoII catalytic inhibitors and suggest substituted acridines may hold promise in treating malignant mesothelioma. Content Type Journal ArticlePages 1-6DOI 10.1007/s10637-011-972... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5070367 Mon, 25 Jul 2011 15:45:24 +0100 5070367 http://www.medworm.com/index.php?rid=5063953&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd1425501736uk313%2F Conclusions PSA declines and stable disease were observed with a combination of sorafenib and bicalutamide including in patients previously progressing on bicalutamide. Strategies to combine multi-targeted kinase inhibitors with hormonal therapies warrant further study in patients with CRPC. Content Type Journal ArticlePages 1-8DOI 10.1007/s10637-011-9722-5Authors Emma K. Beardsley, BC Cancer Agency – Vancouver Cancer Centre, 600 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 4E6Sebastien J. Hotte, Juravinski Cancer Centre, Hamilton, CanadaScott North, Cross Cancer Institute, Edmonton, CanadaSusan L. Ellard, BC Cancer Agency - Cancer Centre for the Southern Interior, Kelowna, CanadaEric Winquist, London Health Sciences Centre, London, CanadaChristian Kollmannsberger, ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5063953 Fri, 22 Jul 2011 17:07:12 +0100 5063953 http://www.medworm.com/index.php?rid=5063954&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0g524m24u0106734%2F Summary  We synthesized a novel hydroxamate-based pan-histone deacetylase inhibitor (HDACI), CG200745 {(E)-2-(Naphthalen-1-yloxymethyl)-oct-2-enedioic acid 1-[(3-dimethylamino-propyl)-amide] 8-hydroxyamide]}. Like other inhibitors, for example vorinostat and belinostat, CG200745 has the hydroxamic acid moiety to bind zinc at the bottom of catalytic pocket. Firstly, we analyzed its inhibitory activity against histone deacetylase (HDAC) in hormone-dependent LNCaP cells and hormone-independent DU145 and PC3 cells. CG200745 inhibited deacetylation of histone H3 and tubulin as much as vorinostat and belinostat did. CG200745 also inhibited growth of prostate cancer cells, increased sub-G1 population, and activated caspase-9, -3 and −8 in LNCaP, DU145 and PC3 cells. These result... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5063954 Tue, 19 Jul 2011 23:38:55 +0100 5063954 http://www.medworm.com/index.php?rid=5063955&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1027235121tp45tx%2F Conclusions In this retrospective analysis remarkably long PFS and OS were obtained with a first-line therapy duration limited to a maximum of 12 cycles. Our data does not support a decreased PFS or increased mortality after discontinuation of bevacizumab in mCRC patients. Content Type Journal ArticlePages 1-6DOI 10.1007/s10637-011-9721-6Authors Gerardo Rosati, Medical Oncology Unit, S. Carlo Hospital, Via P. Petrone, 1, 85100 Potenza, ItalyStefano Cordio, Medical Oncology Unit, Garibaldi Hospital, Catania, ItalyGiuseppe Aprile, Department of Medical Oncology, University Hospital, Udine, ItalyAlfredo Butera, Medical Oncology Unit, S. Giovanni di Dio Hospital, Agrigento, ItalyAntonio Avallone, Department of Gastrointestinal Medical Oncology, National Cancer Institute, Naples, Italy... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5063955 Tue, 19 Jul 2011 06:40:26 +0100 5063955 http://www.medworm.com/index.php?rid=5030618&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj7k12k5k075g8775%2F Summary  The novel AKT inhibitor perifosine possesses myelopoiesis-stimulating effects in rodents. We studied the in vitro effects of the novel agents perifosine, bortezomib and lenalidomide in addition to adriamycin against normal human hematopoietic progenitor cells (HPC) using different clonogenic and non-clonogenic assays. All agents inhibited colony-forming unit (CFU) formation, perifosine inhibiting mainly CFU-granulocyte/macrophage formation and the other agents burst-forming unit-erythroid formation. Perifosine combined with lenalidomide or adriamycin tended to act antagonistically in suppressing CFU formation. Despite their inhibition of CFU formation, perifosine, bortezomib and lenalidomide induced only slight or moderate cytotoxicity in CD34+ selected HPC, as asse... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5030618 Wed, 13 Jul 2011 06:17:29 +0100 5030618 http://www.medworm.com/index.php?rid=5030619&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F21x5836u52677451%2F Conclusions The imiquimod and 5-fluorouracil combination is effective. That patients did not develop new, distant lesions suggests the achievement of locoregional control, probably by the induction of antitumor immune response. Content Type Journal ArticlePages 1-5DOI 10.1007/s10637-011-9717-2Authors Valerie Florin, Department of Dermatology, Claude-Huriez Hospital, University Hospital of Lille, Lille, FranceEve Desmedt, Department of Dermatology, Claude-Huriez Hospital, University Hospital of Lille, Lille, FranceSophie Vercambre-Darras, Department of Dermatology, Claude-Huriez Hospital, University Hospital of Lille, Lille, FranceLaurent Mortier, Department of Dermatology, Claude-Huriez Hospital, University Hospital of Lille, Lille, France Journal Investigational New DrugsOn... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5030619 Tue, 12 Jul 2011 06:12:00 +0100 5030619 http://www.medworm.com/index.php?rid=5030621&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F125l8x71772uu174%2F In this study, a series of seven new quinolinyl acrylate derivatives were synthesized and evaluated against human prostate cancer cells PC-3 and LNCaP in vitro and in vivo. The most effective compound (E)-methyl 2-(7-chloroquinolin-4-ylthio)-3-(4 hydroxyphenyl) acrylate reduced the viability in both cell lines in a time- and dose-dependent manner. Inhibitory effects were also observed on the adhesion, migration, and invasion of the prostate cancer cells as well as on the neoangiogenesis, clonogenic and MMP-9 activity. The effect in vivo was studied in PC-3 xenografts in nude mice. The results were concordant with the in vitro effects and showed decreased tumor growth in treated animals compared to controls. The study suggests the multi-target efficacy of the quinolinyl derivate agai... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5030621 Tue, 12 Jul 2011 06:11:58 +0100 5030621 http://www.medworm.com/index.php?rid=5030620&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9424358gnh113p87%2F Conclusion While treatment with sorafenib did not result in objective responses, patients with biliary cancers receiving this drug had some therapeutic benefit. Additional studies with sorafenib in combination with chemotherapy or other targeted agents may be warranted. Content Type Journal ArticlePages 1-6DOI 10.1007/s10637-011-9719-0Authors Anthony B. El-Khoueiry, University of Southern California/Norris Comprehensive Cancer Center, 1441 Eastlake Ave, Suite 3459, Los Angeles, CA 90033, USACathryn J. Rankin, SWOG Statistical Center, Seattle, WA, USAEdgar Ben-Josef, University of Michigan, Ann Arbor, MI, USAHeinz-Josef Lenz, University of Southern California/Norris Comprehensive Cancer Center, 1441 Eastlake Ave, Suite 3459, Los Angeles, CA 90033, USAPhilip J. Gold, Puget Sound Onc... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5030620 Tue, 12 Jul 2011 06:11:58 +0100 5030620 http://www.medworm.com/index.php?rid=5030622&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg7g4370m12201923%2F Conclusions Figitumumab 20 mg/kg in combination with carboplatin and paclitaxel was well tolerated in chemotherapy-naïve Japanese patients with NSCLC. Further analysis of biomarker data is necessary for the development of figitumumab therapy. Content Type Journal ArticlePages 1-9DOI 10.1007/s10637-011-9715-4Authors Yasushi Goto, Department of Internal Medicine, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 JapanIkuo Sekine, Department of Internal Medicine, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 JapanMaki Tanioka, Department of Internal Medicine, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 JapanTakashi Shibata, Department of Internal Medicine, National Cancer Center Hospital, 5-1-1 Tsukij... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5030622 Tue, 12 Jul 2011 06:11:56 +0100 5030622 http://www.medworm.com/index.php?rid=5020961&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv79q25g104830704%2F Conclusions Inhaled carboplatin could be given as an alternative root of pulmonary drug delivery in selected patients, but further randomized studies remain to prove whether the inhaled chemotherapy is an efficient and safe treatment modality. Content Type Journal ArticlePages 1-13DOI 10.1007/s10637-011-9714-5Authors Paul Zarogoulidis, Aristotle University Pulmonary Department, “G. Papanikolaou” Hospital, Thessaloniki, GreeceEllada Eleftheriadou, Aristotle University Pulmonary Department, “G. Papanikolaou” Hospital, Thessaloniki, GreeceIordanis Sapardanis, Aristotle University Pulmonary Department, “G. Papanikolaou” Hospital, Thessaloniki, GreeceVasiliki Zarogoulidou, Aristotle University Pulmonary Department, “G. Papanikolaou” Hospital, Thessaloniki, GreeceHelliel ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5020961 Fri, 08 Jul 2011 06:29:52 +0100 5020961 http://www.medworm.com/index.php?rid=5010033&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm0j7803660362257%2F Conclusions This study of NK105 (150 mg PTX equivalent/m2) proves the concept for the modest activity and tolerability of a new drug delivery system formulation for PTX. A phase III trial will be evaluated to clarify survival benefit. Content Type Journal ArticlePages 1-7DOI 10.1007/s10637-011-9709-2Authors Ken Kato, Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, 104-0045 Tokyo, JapanKeisho Chin, Department of Cancer Chemotherapy, Cancer Institute Hospital Tokyo, Tokyo, JapanTakaki Yoshikawa, Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, JapanKensei Yamaguchi, Department of Gastroenterology, Saitama Cancer Center, Saitama, JapanYasushi Tsuji, Department of Medical Oncology, Tonan Hospital, Sapporo, Japan... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5010033 Mon, 04 Jul 2011 16:19:33 +0100 5010033 http://www.medworm.com/index.php?rid=5010035&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc2rt741737506684%2F Summary  Two novel dichlorophenyl urea compounds, SR4 and SR9, were synthesized in our laboratory and evaluated for anti-cancer activities. Specifically, we investigated the antiproliferative properties of these new compounds on promyelocytic HL-60 leukemia cells by analyzing their effects on cell differentiation, cell cycle progression and apoptosis. SR4 and SR9 were both cytototoxic to HL-60 cells in a dose-and time-dependent manner, with IC50 of 1.2 μM and 2.2 μM, respectively, after 72 h treatment. Both compounds strongly suppressed growth of HL-60 cells by promoting cell cycle arrest at the G0/G1 transition, with concomitant decrease in protein levels of cyclins D1 and E2 and cyclin-dependent kinases (CDK 2 and CDK 4), and increased protein expression o... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5010035 Mon, 04 Jul 2011 16:19:32 +0100 5010035 http://www.medworm.com/index.php?rid=5010034&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl4106431w4794346%2F Content Type Journal ArticlePages 1-3DOI 10.1007/s10637-011-9712-7Authors Carole Helissey, Service d’oncologie radiothérapie, Hôpital d’Instruction des Armées du Val-de-Grâce, Paris, 75005 FranceCyrus Chargari, Service d’oncologie radiothérapie, Hôpital d’Instruction des Armées du Val-de-Grâce, Paris, 75005 FranceMarion Lahutte, Service de radiologie, Hôpital d’Instruction des Armées du Val-de-Grâce, Paris, 75005 FranceDamien Ricard, Service de neurologie, Hôpital d’Instruction des du Val-de-Grâce, Paris, 75005 FranceLionel Vedrine, Service d’oncologie radiothérapie, Hôpital d’Instruction des Armées du Val-de-Grâce, Paris, 75005 FranceBernard Ceccaldi, Service d’oncologie radiothérapie, Hôpital d’Instruction des Armées du Val-de-Grâce, Paris, 75... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=5010034 Mon, 04 Jul 2011 16:19:32 +0100 5010034 http://www.medworm.com/index.php?rid=4999372&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk00x5r7h84474770%2F Content Type Journal ArticlePages 1-5DOI 10.1007/s10637-011-9707-4Authors Hee Kyung Ahn, Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul, 135-710 Republic of KoreaSoohyeon Lee, Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul, 135-710 Republic of KoreaJong-Mu Sun, Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul, 135-710 Republic of KoreaJeeyun Lee, Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medi... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4999372 Thu, 30 Jun 2011 09:38:00 +0100 4999372 http://www.medworm.com/index.php?rid=4999373&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj03425662gg8259g%2F In this study, we found epigenetic regulation of P-cadherin in human gastric cancer cells that was induced by treatment with DNA demethylating drug and histone deacetylase inhibitor. Silencing P-cadherin by using siRNA induces apoptosis in gastric cells and blocks expression of Tie-2, an angiogenic receptor tyrosine kinase. In contrast, ectopically expressed P-cadherin by generating P-cadherin stable cell line enhances Tie-2 expression and cell mobility. We also demonstrated that inhibition of P-cadherin by PF-03732010, a fully humanized anti-P-cadherin IgG1 monoclonal antibody, suppressed cell migration in vitro and tumor growth in BALB/c nude mice bearing SNU620 gastric cancer xenograft. The data reported here are the first to reveal that the inhibition of P-cadherin decreases tumo... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4999373 Thu, 30 Jun 2011 09:37:58 +0100 4999373 http://www.medworm.com/index.php?rid=4993755&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F52r5jjv4757r2r2m%2F Summary  Selected HIV drugs, either of the protease inhibitor type or the nucleoside antagonist type, have been shown to exert tumoricidal effects. Here, we show that the HIV reverse transcriptase inhibitor Truvada, a combination drug of the cytidine analogue emtricitabine and the adenosine analogue tenofovir, induces DNA damage and cell cycle arrest in human cancer cells. Phosphorylation of the DNA repair enzyme H2AX by emtricitabine/tenofovir indicated that it interfered with the integrity of the DNA and replication machinery in human cancer cells. Long term incubation of cancer cells with emtricitabine/tenofovir caused the formation of multi-nuclear giant cells, further indicating DNA replication problems. When tested as single agents, the anti-tumoral activity of emtric... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4993755 Tue, 28 Jun 2011 15:48:21 +0100 4993755 http://www.medworm.com/index.php?rid=4970515&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1187485101l20541%2F Conclusions Biweekly cetuximab plus irinotecan as second-line treatment showed significant anti-tumor activity in patients with irinotecan-refractory mCRC and WT-KRAS regardless of EGFR expression status. Content Type Journal ArticlePages 1-7DOI 10.1007/s10637-011-9703-8Authors Myoung Joo Kang, Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 86 Asanbyeongwon-gil, Songpa-gu, Seoul, Korea 138–736Yong Sang Hong, Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 86 Asanbyeongwon-gil, Songpa-gu, Seoul, Korea 138–736Kyu-pyo Kim, Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 86 Asanbyeongwon-gil, Songpa-gu, Seoul, Korea 138–736Sun Young Kim, Center for Colorectal Cancer,... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4970515 Fri, 24 Jun 2011 16:00:16 +0100 4970515 http://www.medworm.com/index.php?rid=4970516&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb81277280u015482%2F Conclusions The combination of sorafenib and S-1 showed tolerable toxicity profile and modest clinical efficacy in patients with advanced HCC. The recommended dose of sorafenib and S-1 was 400 mg twice daily and 40 mg/m2 twice daily, respectively. Content Type Journal ArticlePages 1-8DOI 10.1007/s10637-011-9706-5Authors Su Jin Lee, Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135–710 KoreaJeeyun Lee, Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135–710 KoreaSe Hoon Park, Division of Hematology-Oncology, Department of Medicine, Samsung Medical C... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4970516 Tue, 21 Jun 2011 20:55:51 +0100 4970516 http://www.medworm.com/index.php?rid=4946659&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu34g760876n08316%2F Summary  Due to the poor prognosis and limited therapeutic options for adult patients with acute lymphoblastic leukemia (ALL), development of novel therapies is much needed to prolong patient survival and increase the efficacy of their treatment. Malignant T cells need high levels of nutrients to maintain their proliferation rate. Borrelidin, a small molecule nitrile-containing macrolide, is an inhibitor of bacterial and eukaryal threonyl-tRNA synthetase. Borrelidin-mediated inhibition of aminoacyl-tRNA synthesis, leads to an induction in the levels of uncharged tRNA, nutritional stress and ultimately inhibition of protein synthesis. The aim of the present study was to investigate whether borrelidin treatment inhibits the proliferation of malignant ALL cell lines, Jurkat an... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4946659 Thu, 16 Jun 2011 06:29:52 +0100 4946659 http://www.medworm.com/index.php?rid=4946660&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq1564mkg84742g1v%2F This study evaluated the relevance of CXCR2 chemokine receptors in oral squamous cell carcinoma, by means of in vitro and in vivo approaches. The in vitro incubation of the selective and non-peptide CXCR2 receptor antagonist N-(2-hydroxy-4-nitrophenyl)-N9-(2-bromophenyl) Urea (SB225002; 25 to 800 nM) produced a time- and concentration-dependent inhibition of SCC158 (rat) and HN30 (human) cell lines viability. Conversely, this antagonist did not significantly affect the viability of the immortalized keratinocyte lineage, HaCaT. Additionally, the incubation of human IL-8 and rat CINC-1 CXCR2 agonists produced a concentration-related increase on HN30 and SCC158 proliferation. The submucosal injection of SCC158 cells (5 × 106 cells) into the tongue of Fischer 344 rats induced tu... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4946660 Tue, 14 Jun 2011 05:54:55 +0100 4946660 http://www.medworm.com/index.php?rid=4946661&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8023l660222m57v2%2F Conclusions Axitinib (5 mg BID) and gemcitabine (1,000 mg/m2) were well tolerated when administered together, without any pharmacokinetic interactions, and showed encouraging antitumor activity. Content Type Journal ArticlePages 1-9DOI 10.1007/s10637-011-9697-2Authors Jean-Philippe Spano, Groupe Hospitalier Pitié-Salpêtrière, 47-83 Boulevard de l’Hôpital, 75651 Paris Cedex 13, FranceMalcolm J. Moore, Princess Margaret Hospital, Toronto, ON, CanadaYazdi K. Pithavala, Clinical Pharmacology Pfizer Inc, La Jolla, CA, USAAlejandro D. Ricart, Oncology Development Pfizer Inc, La Jolla, CA, USASinil Kim, Oncology Development Pfizer Inc, La Jolla, CA, USAOlivier Rixe, Groupe Hospitalier Pitié-Salpêtrière, 47-83 Boulevard de l’Hôpital, 75651 Paris Cedex 13, France ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4946661 Tue, 14 Jun 2011 05:54:53 +0100 4946661 http://www.medworm.com/index.php?rid=4923340&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv61504718w68p2n5%2F Summary  Malignant pleural mesothelioma is a fatal malignancy linked to asbestos exposure. The main challenge for mesothelioma treatment is to go beyond the drug resistance, in particular against cisplatin (CDDP), one of the most used chemotherapeutic drug. 3-O-methylfunicone (OMF) is a metabolite produced by the fungus Penicillium pinophilum; its antiproliferative properties have been previously studied in vitro. Particularly, OMF is able to inhibit mesothelioma cell motility. To improve the effects of CDDP by-passing the resistance of mesothelioma cells to this drug, in the present study we investigated the combined treatment of OMF with CDDP respectively in an established mesothelioma cell line (NCI) and primary mesothelioma cells (Mest). As compared to the effect of singl... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4923340 Wed, 08 Jun 2011 15:46:26 +0100 4923340 http://www.medworm.com/index.php?rid=4923341&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fbvr04k68u2668777%2F In this study, a third agent was added by in vivo evaluation of a large number of combinations. The addition of octreotide strongly reduced tumor development (T/C% value of 30.2 to 34.5%; P < 0.001) in the same models and prolonged animal survival (P < 0.001) as compared to cisplatin. These results were confirmed in a different laboratory setting using a human xenograft model (NCI-H69, small cell lung cancer). None of these three molecules are known to target DNA. The effectiveness of this combination in several animal models, as well as the low toxicity of these inexpensive drugs, emphasizes the necessity of rapidly setting up a clinical trial. Content Type Journal ArticlePages 1-12DOI 10.1007/s10637-011-9692-7Authors Mohammad Abolhassani, Biorébus, Paris, France... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4923341 Wed, 08 Jun 2011 05:49:34 +0100 4923341 http://www.medworm.com/index.php?rid=4913842&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F65n05837131ux641%2F In conclusion, foretinib appears effective against gastric cancer cells harboring not only MET but also FGFR2 amplification, and exerts its inhibitory effects by blocking inter-RTK signaling networks with MET or FGFR2 at their core. Content Type Journal ArticlePages 1-9DOI 10.1007/s10637-011-9699-0Authors Yu Kataoka, Department of Hospital Pharmacy, Kobe University Hospital, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, JapanToru Mukohara, Department of Medical Oncology/Hematology, Kobe University Hospital, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017 JapanHideo Tomioka, Department of Medical Oncology/Hematology, Kobe University Hospital, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017 JapanYohei Funakoshi, Department of Medical Oncology/Hematology, Kobe University Hospital, 7-5-2, Kusunoki-cho,... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4913842 Tue, 07 Jun 2011 09:39:14 +0100 4913842 http://www.medworm.com/index.php?rid=4913843&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fvmg825227m35078t%2F Summary  Hemiasterlins are cytotoxic tripeptides with antimicrotubule activity originally isolated from marine sponges. We have developed new hemiasterlin derivatives BF65 and BF78 that are highly potent to induce cancer cell death in the low nanomolar range. Examination of their mechanisms of cell cycle arrest and disruption of microtubules revealed an unusual characteristic in addition to anti-tubulin effect. Immunofluorescence staining revealed that A549 lung carcinoma cells treated with BF65 or BF78 exhibited both monopolar and multipolar mitotic spindles. Centrosomes were separated with short spindle microtubules in cells with multipolar spindles. In vitro tubulin polymerization assay confirmed that both BF65 and BF78 were highly potent to inhibit tubulin polymerizatio... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4913843 Tue, 07 Jun 2011 09:39:10 +0100 4913843 http://www.medworm.com/index.php?rid=4904292&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx3483g4t3100nx38%2F Summary  Retinoic acid therapy is nowadays an important component of treatment for residual disease of stage IV neuroblastoma after multimodal therapy. Nevertheless, arising resistance and treatment toxicity could represent relevant limiting factors. In the present study, we show that retinoic acid enhances the cytostatic and apoptogenic properties of the novel adamantyl retinoid ST1926 in a panel of neuroblastoma cells with different p53 status and caspase 8 expression, resulting in synergistic effects as assessed by Combination Index and Isobologram analysis. Under conditions where the two drugs alone produced no toxic effects, their combination resulted in enhanced G2-M arrest and sub-G1 population as shown by BrdU pulse-chase and labeling experiments. PARP cleavage, cas... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4904292 Thu, 02 Jun 2011 06:06:41 +0100 4904292 http://www.medworm.com/index.php?rid=4904293&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe76551x27073442u%2F Summary  Reversible posterior leukoencephalopathy syndrome (RPLS) is a serious condition that manifests as headache, convulsions, visual disturbance, and a characteristic magnetic resonance image (MRI) of the brain. We now describe a case of RPLS that was likely attributable to trastuzumab, a monoclonal antibody against human epidermal growth factor receptor-2 (HER2). Accumulating evidence has shown that molecular targeted agents, especially those with antiangiogenic activity cause significant hypertension which can lead to development of RPLS. Trastuzumab is also shown to inhibit tumor angiogenesis by decreasing the production of VEGF and activating antiangiogenic factors. In a clinical trial of trastuzumab, adverse effects of trastuzumab include hypertension, even though ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4904293 Thu, 02 Jun 2011 06:06:40 +0100 4904293 http://www.medworm.com/index.php?rid=4904294&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fgw3t5361824r53qv%2F Summary  The purpose of this study was to assess the efficacy and safety of bevacizumab plus cetuximab with or without gemcitabine in patients with advanced pancreatic adenocarcinoma. Patients with locally advanced or metastatic pancreatic adenocarcinoma, previously untreated, were randomized to bevacizumab (10 mg/kg q2w) plus cetuximab (400/250 mg/m2 initial/weekly), either with (Arm A) or without (Arm B) gemcitabine (1000 mg/m2 weekly × 3 of 4 weeks). Tumor assessments were performed q8w. Primary study endpoint was progression-free survival (PFS). Sixty-one patients were randomized to Arm A (n = 30) or Arm B (n = 31). Median treatment duration was 9 weeks in Arm A and 8 weeks in Arm B (range, 2.0–40.4). Patients in Arm A had media... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4904294 Wed, 01 Jun 2011 05:48:22 +0100 4904294 http://www.medworm.com/index.php?rid=4904295&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F082h562142842m20%2F Content Type Journal ArticlePages 1-5DOI 10.1007/s10637-011-9695-4Authors Maria Grazia di Iasio, Department of Morphology and Embryology and LTTA Centre, University of Ferrara, Ferrara, ItalyRiccardo Addobbati, Institute for Maternal and Child Health, IRCCS “Burlo Garofolo”, Trieste, ItalyOriano Radillo, Institute for Maternal and Child Health, IRCCS “Burlo Garofolo”, Trieste, ItalyRebecca Voltan, Department of Morphology and Embryology and LTTA Centre, University of Ferrara, Ferrara, Italy Journal Investigational New DrugsOnline ISSN 1573-0646Print ISSN 0167-6997 (Source: Investigational New Drugs) Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4904295 Mon, 30 May 2011 16:55:01 +0100 4904295 http://www.medworm.com/index.php?rid=4904296&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F64tx624301g050g7%2F Conclusion Application of the two-stage model-based trial design in Phase I programs with novel anti-cancer drugs that cause haematological toxicity is feasible, safe, and may lead to a reduction in the number of patient treated at sub-therapeutic dose-levels. Content Type Journal ArticlePages 1-12DOI 10.1007/s10637-011-9694-5Authors Ron J. Keizer, Department of Pharmacy & Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The NetherlandsAnthe S. Zandvliet, Department of Pharmacy & Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The NetherlandsJos H. Beijnen, Department of Pharmacy & Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterda... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4904296 Fri, 27 May 2011 18:13:12 +0100 4904296 http://www.medworm.com/index.php?rid=4904297&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4657117417p42964%2F Conclusions Our data suggest that bevacizumab 7.5 mg/kg can be safely infused over 10 min in unselected NSCLC patients despite their cardio-vascular and respiratory comorbidities, saving time for both patients and caregivers. Content Type Journal ArticlePages 1-5DOI 10.1007/s10637-011-9690-9Authors Olivier Mir, Department of Medical Oncology, CERIA (Centre for Research on Angiogenesis Inhibitors), Paris, FranceJérôme Alexandre, Department of Medical Oncology, CERIA (Centre for Research on Angiogenesis Inhibitors), Paris, FranceRomain Coriat, Department of Medical Oncology, CERIA (Centre for Research on Angiogenesis Inhibitors), Paris, FranceStanislas Ropert, Department of Medical Oncology, CERIA (Centre for Research on Angiogenesis Inhibitors), Paris, FrancePascaline Bo... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4904297 Wed, 25 May 2011 16:01:20 +0100 4904297 http://www.medworm.com/index.php?rid=4904298&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn3j25x421088741r%2F Conclusion Cediranib (20 or 30 mg) in combination with mFOLFOX6 was considered tolerable according to the protocol-defined criteria, providing justification for the Phase II part of this study. Content Type Journal ArticlePages 1-8DOI 10.1007/s10637-011-9693-6Authors Taroh Satoh, Kinki University School of Medicine, Osaka, JapanKensei Yamaguchi, Saitama Cancer Centre, Saitama, JapanNarikazu Boku, St. Marianna University School of Medicine, Kanagawa, JapanWataru Okamoto, Kinki University School of Medicine, Osaka, JapanTomotaka Shimamura, Saitama Cancer Centre, Saitama, JapanKentaro Yamazaki, Shizuoka Cancer Centre, Shizuoka, JapanXiaojin Shi, AstraZeneca KK, Osaka, JapanHideyuki Mishima, National Hospital Organization, Osaka National Hospital, Osaka, Japan Journal Inves... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4904298 Tue, 24 May 2011 16:05:11 +0100 4904298 http://www.medworm.com/index.php?rid=4854487&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft2tl6056147223r3%2F Content Type Journal ArticlePages 1-6DOI 10.1007/s10637-011-9688-3Authors Sarah Schott, Department of Gynaecology and Obstetrics, National Center for Tumour Diseases (NCT), University of Heidelberg, 69115 Heidelberg, GermanyMarkus Wallwiener, Department of Gynaecology and Obstetrics, National Center for Tumour Diseases (NCT), University of Heidelberg, 69115 Heidelberg, GermanyBeate Kootz, Department of Gynaecology and Obstetrics, University of Tuebingen, 72076 Tuebingen, GermanyHarald Seeger, Department of Gynaecology and Obstetrics, University of Tuebingen, 72076 Tuebingen, GermanyTanja Fehm, Department of Gynaecology and Obstetrics, University of Tuebingen, 72076 Tuebingen, GermanyHans Neubauer, Department of Gynaecology and Obstetrics, University of Tuebingen, 72076 Tuebingen, Germa... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4854487 Fri, 20 May 2011 16:05:31 +0100 4854487 http://www.medworm.com/index.php?rid=4854488&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa95135w723w30k47%2F Content Type Journal ArticlePages 1-2DOI 10.1007/s10637-011-9684-7Authors Timothy P. Burkholder, Discovery Chemistry Research and Technology, Eli Lilly and Company, Indianapolis, IN, USAJoshua R. Clayton, Discovery Chemistry Research and Technology, Eli Lilly and Company, Indianapolis, IN, USAMark E. Rempala, Discovery Chemistry Research and Technology, Eli Lilly and Company, Indianapolis, IN, USAJames R. Henry, Discovery Chemistry Research and Technology, Eli Lilly and Company, Indianapolis, IN, USAJohn M. Knobeloch, Discovery Chemistry Research and Technology, Eli Lilly and Company, Indianapolis, IN, USADavid Mendel, Discovery Chemistry Research and Technology, Eli Lilly and Company, Indianapolis, IN, USAJohnathan A. McLean, Discovery Chemistry Research and Technology, Eli Lilly and ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4854488 Thu, 19 May 2011 16:33:21 +0100 4854488 http://www.medworm.com/index.php?rid=4854489&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0w046gx5744u43n0%2F This study compared selumetinib with capecitabine in patients with advanced or metastatic pancreatic cancer who had been pretreated with a gemcitabine-based regimen. In this randomized, multicenter phase II study (NCT00372944), patients received either 100 mg oral selumetinib twice daily or 1,250 mg/m2 oral capecitabine twice daily for 2 weeks followed by a 1-week break, given in 3-weekly cycles. The primary endpoint was overall survival. In all 70 patients were randomized. The median survival was 5.4 months in the selumetinib group and 5.0 months in the capecitabine group (hazard ratio 1.03; two-sided 80% confidence interval = 0.68,1.57; P = 0.92). Disease progression events occurred in 84% and 88% of patients in the selumetinib and capecitabine treat... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4854489 Wed, 18 May 2011 18:19:23 +0100 4854489 http://www.medworm.com/index.php?rid=4854490&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv4286257326571wm%2F Content Type Journal ArticlePages 1-7DOI 10.1007/s10637-011-9686-5Authors Felix Kratz, Tumor Biology Center, Department of Medical Oncology, Clinical Research, Breisacher Strasse 117, 79106 Freiburg, GermanyIduna Fichtner, Max-Delbrück Center, Robert-Rössle-Strasse 10, 13122 Berlin, GermanyRalph Graeser, ProQinase GmbH, Breisacher Strasse 117, 79106 Freiburg, Germany Journal Investigational New DrugsOnline ISSN 1573-0646Print ISSN 0167-6997 (Source: Investigational New Drugs) Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4854490 Wed, 18 May 2011 06:16:05 +0100 4854490 http://www.medworm.com/index.php?rid=4854491&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu0thg216rh816265%2F Conclusions Further development of olaparib and topotecan in combination was not explored due to dose-limiting hematological AEs and the resulting sub-therapeutic MTD. Content Type Journal ArticlePages 1-8DOI 10.1007/s10637-011-9682-9Authors Jens Samol, St George’s Hospital, Blackshaw Rd, London, UKMalcolm Ranson, Christie Hospital NHS Trust, Wilmslow Road, Manchester, UKEdwina Scott, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UKEuan Macpherson, AstraZeneca, Alderley Park, Macclesfield, UKJames Carmichael, AstraZeneca, Alderley Park, Macclesfield, UKAnne Thomas, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UKJames Cassidy, The Beatson West of Scotland Cancer Centre, 1053 Great Western Road, ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4854491 Wed, 18 May 2011 06:16:04 +0100 4854491 http://www.medworm.com/index.php?rid=4831821&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4p08535506357816%2F Summary  Salinomycin (Sal) is potentially useful for the treatment of cancer. The present study examined a novel mechanism of Sal sensitization in cancer cells. Sal sensitized radiation-treated cancer cells by inducing G2 arrest and causing DNA damage. Sal treatment also reduced p21 levels in radiation-treated cells. Considering that Sal sensitizes doxorubicin (DOX)- or etoposide (ETO)-treated cancer cells by causing DNA damage and reducing p21 expression, the results from our study suggest that the mechanism underlying Sal sensitization is conserved in both chemo- and radiation-treated cells. We also tested the ability of Sal to inhibit p-glycoprotein (P-gp), which plays a role in the efflux of anti-cancer drugs to reduce cellular damage. In particular, we compared Sal to ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4831821 Sat, 14 May 2011 15:58:29 +0100 4831821 http://www.medworm.com/index.php?rid=4831820&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc013r7575m211125%2F This article provides an overview of the angiogenic mechanisms implicated in RCC, focusing on the main vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and mammalian target of rapamycin (mTOR) signalling pathways. Targeted antiangiogenic agents for the treatment of mRCC include receptor tyrosine kinase inhibitors (such as sunitinib, sorafenib, pazopanib, axitinib, cediranib and tivozanib), monoclonal antibodies (such as bevacizumab) and mTOR inhibitors (such as temsirolimus and everolimus). In this article, we consider the modes of action of these targeted agents and their differing target receptor profiles and we also evaluate how these correlate with their clinical efficacy and tolerability profiles. Content Type Journal ArticlePages 1-11DOI 10.... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4831820 Sat, 14 May 2011 15:58:29 +0100 4831820 http://www.medworm.com/index.php?rid=4831822&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp1g2441m50837022%2F Summary  TSU-68 is a novel multiple tyrosine kinase inhibitor that inhibits VEGFR-2, FGF and PDGF receptors. We conducted a phase I study to evaluate the safety and pharmacokinetic of TSU-68 when used with S-1 and oxaliplatin (SOX) in metastatic colorectal cancer (mCRC) patients. Patients with mCRC were treated with TSU-68 200 mg (Level 1) or 400 mg (Level 2) b.i.d. daily, S-1 35 mg/m2 b.i.d. on Days 1–14 and oxaliplatin 130 mg/m2 i.v. on Day 1 repeatedly every 3 weeks. Of eleven patients enrolled, two patients were excluded from dose limiting toxicity (DLT) assessment. Six patients at Level 1 experienced no DLT. Of three patients at Level 2, two patients experienced DLTs (one patient: grade 3 hiccup and palmar-plantar erythrodysaesthesia syndrome,... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4831822 Thu, 12 May 2011 16:45:05 +0100 4831822 http://www.medworm.com/index.php?rid=4831823&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn868475k5g3372n4%2F In conclusion, the novel DNA-PKcs inhibitor, ICC, synergistically sensitized 3 breast cancer cell lines to doxorubicin and cisplatin. Enhanced efficacy of doxorubicin was achieved by inhibiting non-homologous end joining resulting in increased accumulation of DNA damage. Content Type Journal ArticlePages 1-7DOI 10.1007/s10637-011-9678-5Authors David Davidson, Montreal Centre for Experimental Therapeutics in Cancer—Segal Cancer Center—Lady Davis Institute—Jewish General Hospital, McGill University, 3755, Côte Sainte Catherine Road, Montréal, Québec H3T 1E2, CanadaJeremy Grenier, Montreal Centre for Experimental Therapeutics in Cancer—Segal Cancer Center—Lady Davis Institute—Jewish General Hospital, McGill University, 3755, Côte Sainte Catherine Road, Montréal, Qué... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4831823 Thu, 12 May 2011 16:45:03 +0100 4831823 http://www.medworm.com/index.php?rid=4822200&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F62132v79ph3648uw%2F Summary  Gliomas are the most common primary brain tumor, and their treatment is still a challenge. Here, we evaluated the antiproliferative effect of a novel combination of two potent oxidative stress enhancers: menadione (M) and sodium orthovanadate (SO). We observed both short-term and prolonged growth inhibitory effects of M or SO alone as well as in combination (M:SO) on DBTRG.05MG human glioma cells. A stronger antiproliferative effect was observed in the short-term proliferation assay with the M:SO combination compared to either investigated agent alone. In the long-term proliferation assay, a 10-day exposure to M:SO at concentrations of 10 μM:17.5 μM or 17.5 μM:10 μM was enough to kill 100% of the cells; no cell regrowth was observed after re-... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4822200 Mon, 09 May 2011 05:34:57 +0100 4822200 http://www.medworm.com/index.php?rid=4806129&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F35680744u5xjq344%2F Conclusion Dasatinib is inactive as a single agent in previously treated metastatic CRC patients. Content Type Journal ArticlePages 1-5DOI 10.1007/s10637-011-9681-xAuthors Manish R. Sharma, Section of Hematology/Oncology, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL 60637-1470, USAKristen Wroblewski, Department of Health Studies, University of Chicago, Chicago, IL, USABlase N. Polite, Section of Hematology/Oncology, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL 60637-1470, USAJames A. Knost, Illinois Cancer Care, Peoria, IL, USAJames A. Wallace, Section of Hematology/Oncology, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL 60637-1470, USASanjiv Modi, Joliet Hematology/Oncology, Joliet, IL, USABethany G. Sleckman, S... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4806129 Fri, 06 May 2011 16:18:52 +0100 4806129 http://www.medworm.com/index.php?rid=4806130&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F65625181w51725xr%2F Summary  Recent research suggests that altered redox control of melanoma cell survival, proliferation, and invasiveness represents a chemical vulnerability that can be targeted by pharmacological modulation of cellular oxidative stress. The endoperoxide artemisinin and semisynthetic artemisinin-derivatives including dihydroartemisinin (DHA) constitute a major class of antimalarials that kill plasmodium parasites through induction of iron-dependent oxidative stress. Here, we demonstrate that DHA may serve as a redox chemotherapeutic that selectively induces melanoma cell apoptosis without compromising viability of primary human melanocytes. Cultured human metastatic melanoma cells (A375, G361, LOX) were sensitive to DHA-induced apoptosis with upregulation of cellular oxidati... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4806130 Thu, 05 May 2011 15:48:22 +0100 4806130 http://www.medworm.com/index.php?rid=4806131&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd7u05n3xk2212437%2F Discussion We felt it was our obligation to share this interrupted phase II study for two reasons: to report the fate of camptothecin glycoconjugate and to report the unique situation of a clinical hold during a phase II study. Content Type Journal ArticlePages 1-3DOI 10.1007/s10637-011-9679-4Authors Marije Slingerland, Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The NetherlandsHans Gelderblom, Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands Journal Investigational New DrugsOnline ISSN 1573-0646Print ISSN 0167-6997 (Source: Investigational New Drugs) Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4806131 Thu, 05 May 2011 15:48:21 +0100 4806131 http://www.medworm.com/index.php?rid=4790400&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F03140t5g778j3424%2F Content Type Journal ArticlePages 1-5DOI 10.1007/s10637-011-9675-8Authors Erika Rimondi, Department of Morphology and Embryology and LTTA Centre, University of Ferrara, Ferrara, ItalyMaria Grazia di Iasio, Department of Morphology and Embryology and LTTA Centre, University of Ferrara, Ferrara, ItalyArianna Gonelli, Department of Morphology and Embryology and LTTA Centre, University of Ferrara, Ferrara, ItalyClaudio Celeghini, Institute for Maternal and Child Health, IRCCS “Burlo Garofolo”, Trieste, ItalyPaola Secchiero, Department of Morphology and Embryology and LTTA Centre, University of Ferrara, Ferrara, ItalyGiorgio Zauli, Institute for Maternal and Child Health, IRCCS “Burlo Garofolo”, Trieste, Italy Journal Investigational New DrugsOnline ISSN 1573-0646Print ISSN 0... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4790400 Tue, 03 May 2011 19:46:45 +0100 4790400 http://www.medworm.com/index.php?rid=4782741&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7u3u258814284qn1%2F Conclusions The combination of nab-paclitaxel (100 mg/m2) administered weekly and carboplatin at an AUC of 6 every 3 weeks was well tolerated in Japanese patients with advanced NSCLC. This combination therapy also showed promising antitumor activity and was not associated with relevant pharmacokinetic interactions. Content Type Journal ArticlePages 1-6DOI 10.1007/s10637-011-9674-9Authors Isamu Okamoto, Department of Medical Oncology, Kinki University Faculty of Medicine, 377–2 Ohno-higashi, Osaka-Sayama, Osaka 589–8511, JapanNobuyuki Yamamoto, Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, JapanKaoru Kubota, Divisions of Thoracic Oncology, National Cancer Center Hospital East, Chiba, JapanYuichiro Ohe, Department of Medical Oncology, National Cancer ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4782741 Mon, 02 May 2011 14:58:50 +0100 4782741 http://www.medworm.com/index.php?rid=4782743&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe372452929147l57%2F Content Type Journal ArticlePages 1-1DOI 10.1007/s10637-011-9664-yAuthors Joseph A. Bauer, Bauer Research Foundation, Akron Innovation Campus, 411 Wolf Ledges Pkwy, suite 105, Akron, OH 44311, USAGerald Frye, PetsDx Veterinary Imaging, Pittsburgh, PA 15237, USAAnne Bahr, PetRays Veterinary Radiology Consultants, Spring, TX 77386, USAJennifer Gieg, Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, OH 43210, USAPeter Brofman, Carolina Veterinary Specialists Medical Center, Charlotte, NC 28273, USA Journal Investigational New DrugsOnline ISSN 1573-0646Print ISSN 0167-6997 (Source: Investigational New Drugs) Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4782743 Mon, 02 May 2011 14:58:49 +0100 4782743 http://www.medworm.com/index.php?rid=4782742&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn251g14km8318838%2F Summary  Cancer stem cells (CSC) are chemoresistant and implicated in tumor recurrence, metastasis and high patient mortality; thus substances impairing CSC activity, could be invaluable as novel cancer therapeutics. We previously showed that CAPE (caffeic acid phenethyl ester), a component of propolis, a honeybee product, inhibits growth of MDA-MB-231 (MDA-231) cells, mdr gene expression, NF-κB, EGFR, and VEGF. We hypothesized that CAPE also acts by interfering with CSC-mediated effects. We isolated breast CSC (bCSC) from MDA-231 cells, a model of human triple-negative breast cancer, and mouse xenografts. bCSC grow as mammospheres (MMS) and when dissociated into single cells, form MMS again, a sign of self-renewal. bCSC exhibited the characteristic CD44+/CD24-/low phenotyp... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4782742 Mon, 02 May 2011 14:58:49 +0100 4782742 http://www.medworm.com/index.php?rid=4782744&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fpj41108702642122%2F Conclusion Eribulin was well tolerated but did not result in any objective responses in gemcitabine refractory pancreatic cancer. However, several patients had prolonged stable disease, suggesting that further studies of eribulin in pancreatic cancer may be warranted. Content Type Journal ArticlePages 1-5DOI 10.1007/s10637-011-9673-xAuthors Daniel J. Renouf, University Health Network-Princess Margaret Hospital, Toronto, ON, CanadaPatricia A. Tang, Tom Baker Cancer Centre, Calgary, AB, CanadaPierre Major, Juravinski Cancer Centre, Hamilton, ON, CanadaMonika K. Krzyzanowska, University Health Network-Princess Margaret Hospital, Toronto, ON, CanadaBindi Dhesy-Thind, Juravinski Cancer Centre, Hamilton, ON, CanadaJohn R. Goffin, Juravinski Cancer Centre, Hamilton, ON, CanadaDavid Hedley... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4782744 Wed, 27 Apr 2011 08:45:19 +0100 4782744 http://www.medworm.com/index.php?rid=4771993&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh34w877732506j21%2F Summary  The efficacy of anti-CD33 immunoconjugates had been previously demonstrated for gemtuzumab-ozogamicin. AVE9633 is an anti-CD33-maytansine conjugate created by ImmunoGen Inc. Phase I trials of AVE9633 were performed in patients with AML to evaluate tolerability, pharmacokinetics and pharmacodynamics. Three phase I studies of AVE9633 were performed in 54 patients with refractory/relapsed AML, evaluating drug infusion on day 1 of a 21-day cycle (Day 1 study), day 1 and 8 (Day 1/8 study) and day 1, 4 and 7 (Day 1/4/7 study) of a 28-day cycle. Toxicity was mainly allergic reaction during infusion (3 grade 3 bronchospasms). DLT was reached for the D1–D7 schedule at 150 mg/sqm (1 keratitis, 1 liver toxicity), and the MTD was set at 130 mg/sqm for this schedule.... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4771993 Mon, 25 Apr 2011 16:42:06 +0100 4771993 http://www.medworm.com/index.php?rid=4748743&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd016733116706864%2F Conclusion The incidence of renal toxicity in phase I pts treated with antiangiogenic compounds was much higher than expected. Simple screening of Cr levels appears to be insufficient and careful nephrologic monitoring at baseline and during treatment should be implemented in early clinical trials assessing the risk/benefit ratio of new antiangiogenic compounds. Content Type Journal ArticlePages 1-5DOI 10.1007/s10637-011-9671-zAuthors Antonin Levy, SITEP (Service des Innovations Therapeutiques Precoces), Department of Medicine, Institut Gustave Roussy, Paris XI University, 114 rue Edouard Vaillant, 94805 Villejuif, FranceLaurence Albiges-Sauvin, SITEP (Service des Innovations Therapeutiques Precoces), Department of Medicine, Institut Gustave Roussy, Paris XI University, 114 rue Ed... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4748743 Thu, 21 Apr 2011 06:08:19 +0100 4748743 http://www.medworm.com/index.php?rid=4748744&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv100t54481531371%2F In conclusion, the PDT potency of the prodrugs was in the order: AlaAcBu, AlaAcPi > AlaFaBu ≥ ALA > AlaFaPi, and the superiority of AlaAcBu stems from lower molar concentrations of AlaAcBu and lower light intensity needed to activate cell death following PDT. Content Type Journal ArticlePages 1-11DOI 10.1007/s10637-011-9669-6Authors Gili Berkovitch-Luria, The Mina and Everard Goodman Life Sciences Faculty, Bar Ilan University, Ramat Gan, 52900 IsraelMichal Weitman, Chemistry Department, Bar Ilan University, Ramat Gan, IsraelAbraham Nudelman, Chemistry Department, Bar Ilan University, Ramat Gan, IsraelAda Rephaeli, Laboratory of Pharmacology and Experimental Oncology, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, IsraelZvi ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4748744 Thu, 21 Apr 2011 06:08:18 +0100 4748744 http://www.medworm.com/index.php?rid=4748745&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc8v260731n36175g%2F Content Type Journal ArticlePages 1-6DOI 10.1007/s10637-011-9672-yAuthors Veronica Marchetti, Department of Veterinary Clinics, Veterinary Teaching Hospital, University of Pisa, Pisa, ItalyMario Giorgi, Department of Veterinary Clinics, Veterinary Teaching Hospital, University of Pisa, Pisa, ItalyAnna Fioravanti, Division of Pharmacology, Department of Internal Medicine, Faculty of Medicine and Surgery, University of Pisa, Via Roma, 55, I-56126 Pisa, ItalyRiccardo Finotello, Department of Veterinary Clinics, Veterinary Teaching Hospital, University of Pisa, Pisa, ItalySimonetta Citi, Department of Veterinary Clinics, Veterinary Teaching Hospital, University of Pisa, Pisa, ItalyBastianina Canu, Division of Pharmacology, Department of Internal Medicine, Faculty of Medicine and Surgery, U... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4748745 Thu, 21 Apr 2011 06:08:17 +0100 4748745 http://www.medworm.com/index.php?rid=4725816&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk3020501m5670667%2F Summary  Cartilage tumours present ongoing therapeutic challenges due to their chondrogenic extracellular matrix that potentially hampers drug delivery, their low percentage of dividing cells, and their poor vascularity. In this context, and based on the affinity of the quaternary ammonium moiety for proteoglycans (PG), we developed a strategy that uses the quaternary ammonium function to selectively deliver DNA alkylating agents to the cartilage tumour tissue. We engineered the quaternary ammonium derivative of melphalan (Mel-AQ) and assessed its antitumoural activity in vitro and in vivo. In vitro, micromolar concentrations of Mel-AQ inhibited the proliferation of human HEMC-SS chondrosarcoma and Saos-2 osteosarcoma cell lines. Moreover, 24-h incubation with 20 μM M... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4725816 Fri, 15 Apr 2011 15:49:39 +0100 4725816 http://www.medworm.com/index.php?rid=4725817&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm855hr51p3216331%2F Summary  Eg5 (kinesin spindle protein) is a microtubule motor protein, essential for centrosome separation during mitosis. This Phase I/II, open-label, multicenter, two-part study investigated AZD4877, a potent Eg5 inhibitor, in patients with acute myeloid leukemia. Primary objectives were to determine the maximum tolerated dose (MTD) (part A), assess efficacy (part B) and determine the pharmacokinetic profile (parts A and B). Secondary objectives included assessment of safety and tolerability. AZD4877 was administered at a range of doses (2, 4, 7, 10, 13, 16 and 18 mg/day) as a 1-hour intravenous infusion on three consecutive days of a continuous 2-week schedule. The MTD in part A was defined as 16 mg/day based on dose-limiting stomatitis at 16 and 18 mg/day... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4725817 Thu, 14 Apr 2011 17:01:49 +0100 4725817 http://www.medworm.com/index.php?rid=4725818&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd332286245853lu8%2F Summary  The natural compound pancratistatin (PST), isolated from the Hymenocallis littoralis plant, specifically induces apoptosis in many cancer cell lines. Unlike many other chemotherapeutics, PST is not genotoxic and has minimal adverse effects on non-cancerous cells. However, its availability for preclinical and clinical work is limited due to its low availability in its natural source and difficulties in its chemical synthesis. Several synthetic analogues of 7-deoxypancratistatin with different modifications at C-1 were synthesized and screened for apoptosis inducing activity in human colorectal cancer (CRC) cells. We found that a C-1 acetoxymethyl derivative of 7-deoxypancratistatin, JC-TH-acetate-4 (JCTH-4), was effective in inducing apoptosis in both p53 positive (H... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4725818 Thu, 14 Apr 2011 17:01:48 +0100 4725818 http://www.medworm.com/index.php?rid=4710334&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh74g1358577r376p%2F Conclusion Single-agent trabectedin treatment was reasonably well tolerated. Trabectedin can be administered for prolonged periods to patients with sustained clinical benefit (induction of disease stability or shrinkage) without cumulative toxicities over time. Content Type Journal ArticlePages 1-10DOI 10.1007/s10637-011-9662-0Authors Axel Le Cesne, Department of Medicine, Institut Gustave Roussy, 94805 Villejuif Cedex, FranceAlejandro Yovine, Hôpital St Louis, Paris, FranceJean-Yves Blay, Centre Léon Bérard, Lyon, FranceSuzette Delaloge, Department of Medicine, Institut Gustave Roussy, 94805 Villejuif Cedex, FranceRobert G. Maki, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY, USAJean-Louis Misset, Hôpital St Louis, Paris, FrancePilar Frontelo... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4710334 Mon, 11 Apr 2011 15:45:34 +0100 4710334 http://www.medworm.com/index.php?rid=4710335&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F904411p024638101%2F Conclusions Efficacy data of PFS and OS are at least comparable to gemcitabine, the current standard of care. S-1 is active in Caucasian patients with metastatic PC. Content Type Journal ArticlePages 1-9DOI 10.1007/s10637-011-9665-xAuthors Beate Schultheis, Department of Haematology and Medical Oncology, University of Bochum (Marienhospital Herne), Herne, GermanyDirk Strumberg, Department of Haematology and Medical Oncology, University of Bochum (Marienhospital Herne), Herne, GermanyLothar Bergmann, Department of Haematology and Medical Oncology, Johann Wolfgang Goethe-University, Frankfurt/Main, GermanyUllrich Graeven, Kliniken Maria Hilf, Mönchengladbach, GermanyAxel-Rainer Hanauske, Hospital St. Georg, Hamburg, GermanyRainer Lipp, Department of Haematology and Medical Oncology,... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4710335 Mon, 11 Apr 2011 15:45:30 +0100 4710335 http://www.medworm.com/index.php?rid=4710336&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1k245848g3556838%2F Conclusion Panobinostat administered orally once daily on Monday, Wednesday, and Friday of each week was well tolerated at doses up to 20 mg in Japanese patients. Dose escalation did not proceed after exploration of the 20 mg dose due to emerging global clinical data at that time. Content Type Journal ArticlePages 1-11DOI 10.1007/s10637-011-9666-9Authors Akira Fukutomi, Shizuoka Cancer Center, Shizuoka, JapanKiyohiko Hatake, Cancer Institute Hospital, Tokyo, JapanKaoru Matsui, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, JapanSakura Sakajiri, Cancer Institute Hospital, Tokyo, JapanTomonori Hirashima, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, JapanHiromi Tanii, Novartis Pharma K.K., Tokyo, JapanKen Kob... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4710336 Mon, 11 Apr 2011 15:45:25 +0100 4710336 http://www.medworm.com/index.php?rid=4686593&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F622hj66h636202t2%2F Summary  Several phenylaminopyrimidoisoquinolinequinones (APIQs) were tested for their cytotoxicity against different cancer cell lines (K562, T24, HepG2) in the presence or absence of ascorbate. Ascorbate enhanced the toxic effects of quinones with first half-wave potential EI 1/2 values in the range of −480 to −660 mV. Phenylaminoquinones that were unsubstituted at position 6 exhibited greater cytotoxic activity than did their 6-methyl-substituted analogues. Two groups of compounds were further selected, namely 8–10 and 20–22, to study the cellular mechanisms involved in quinone cytotoxicity. Indeed, these compounds have the same range of redox potentials but differed considerably in their capacity to induce cell death. In the presence of ascorbate, the cell d... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4686593 Tue, 05 Apr 2011 09:59:22 +0100 4686593 http://www.medworm.com/index.php?rid=4665180&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh8283w3573734m20%2F In conclusion, SB-T-1214, SB-T-12854 and IDN5109 are good candidates for further study. Content Type Journal ArticlePages 1-12DOI 10.1007/s10637-011-9654-0Authors Berta Otová, Institute of Biology and Medical Genetics, 1st Faculty of Medicine and General Teaching Hospital Charles University, 128 00 Prague, Czech RepublicIwao Ojima, Institute of Chemical Biology & Drug Discovery, State University of New York at Stony Brook, New York, NY, USARadka Václavíková, Toxicogenomics Unit, National Institute of Public Health, 100 42 Prague, Czech RepublicJiří Hrdý, Institute of Biology and Medical Genetics, 1st Faculty of Medicine and General Teaching Hospital Charles University, 128 00 Prague, Czech RepublicMarie Ehrlichová, Toxicogenomics Unit, National Institute of Public Health, 1... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4665180 Tue, 29 Mar 2011 17:35:26 +0100 4665180 http://www.medworm.com/index.php?rid=4665181&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa592m7m0n424r822%2F Summary  Both, DNA methylation and histone deacetylation play a crucial role in cancer development by silencing the expression of specific tumour suppressor genes. Several studies describe the use of combinations of DNA methyltransferase inhibitors (DNMT-i) and histone deacetylase inhibitors (HDAC-i) as an improved strategy to treat neoplasms. However, no information is available concerning their biological impact on healthy, non-malignant cells, including hepatocytes. Therefore, the effects of the combination of the DNMT-i decitabine (DAC) with the HDAC-i 6-[(4-pyrrolidine-1-ylbenzoyl) amino] hexanoic acid hydroxamate (AN-8) on cell proliferation and differentiation were examined in primary rat hepatocyte cultures. We found that, upon simultaneous exposure of the cells to ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4665181 Tue, 29 Mar 2011 07:06:48 +0100 4665181 http://www.medworm.com/index.php?rid=4632444&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft7513235k5066478%2F Conclusions Neither sorafenib alone or sorafenib in combination with gemcitabine manifested promising activity in metastatic pancreatic cancer. Content Type Journal ArticlePages 1-9DOI 10.1007/s10637-011-9658-9Authors A. B. El-Khoueiry, Division of Medical Oncology, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Ave, Suite 3440, Los Angeles, CA 90033, USAR. K. Ramanathan, University of Pittsburgh Cancer Institute, Pittsburgh, PA USAD. Y. Yang, Department of Preventive Medicine, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA USAW. Zhang, Division of Medical Oncology, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern Califor... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4632444 Mon, 21 Mar 2011 18:58:34 +0100 4632444 http://www.medworm.com/index.php?rid=4632446&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2607497u1024v07t%2F In conclusion, potent antitumour efficacy and low toxicity of new compounds in comparison with the common chemotherapy drug 5-FU make them promising anticancer agents. Additional pre-clinical and clinical studies are warranted to illuminate the mode of action of these newly synthesized compounds in vivo, which would lay the groundwork for their further optimization. Content Type Journal ArticlePages 1-10DOI 10.1007/s10637-011-9657-xAuthors Jelena Kašnar-Šamprec, German Heart Center, Technical University Munich, Lazarettstraße 36, 80636 Munich, GermanyIvana Ratkaj, Department of Biotechnology, University of Rijeka, Trg braće Mažuranića 10, 51000 Rijeka, CroatiaKatarina Mišković, Laboratory of Functional Genomics, School of Medicine, J. J. Strossmayer University of Osijek, ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4632446 Mon, 21 Mar 2011 18:58:33 +0100 4632446 http://www.medworm.com/index.php?rid=4632445&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fauq777483h7320t3%2F Conclusions MK-0731 at the MTD of 17 mg/m2/day every 21 days in patients with solid tumors had few grade 3 and 4 toxicities with the major DLTs at higher doses being myelosuppression. Anti-tumor efficacy was suggested by the length of stable disease in selected patients with taxane-resistant tumors. Content Type Journal ArticlePages 1-8DOI 10.1007/s10637-011-9653-1Authors Kyle Holen, University of Wisconsin Carbone Cancer Center, 600 Highland Ave., Madison, WI 53792–5666, USARobert DiPaola, Cancer Institute of New Jersey, New Brunswick, NJ USAGlenn Liu, University of Wisconsin Carbone Cancer Center, 600 Highland Ave., Madison, WI 53792–5666, USAAntoinette R. Tan, Cancer Institute of New Jersey, New Brunswick, NJ USAGeorge Wilding, University of Wisconsin Carbone Canc... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4632445 Mon, 21 Mar 2011 18:58:33 +0100 4632445 http://www.medworm.com/index.php?rid=4632447&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F90717l38734986nx%2F In this study we investigated the molecular mediators of the anti-ovarian cancer activity of the structurally related antiprogestins RU-38486, ORG-31710 and CDB-2914. We studied the responses of wt p53 OV2008 and p53 null SK-OV-3 cells to varying doses of RU-38486, ORG-31710 and CDB-2914. The steroids inhibited the growth of both cell lines with a potency of RU-38486 > ORG-31710 > CDB-2914, and were cytostatic at lower doses but lethal at higher concentrations. Antiprogestin-induced lethality associated with morphological features of apoptosis, hypodiploid DNA content, DNA fragmentation, and cleavage of executer caspase substrate PARP. Cell death ensued despite RU-38486 caused transient up-regulation of anti-apoptotic Bcl-2, ORG-31710 induced transient up-regulation of inhibito... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4632447 Mon, 21 Mar 2011 18:58:31 +0100 4632447 http://www.medworm.com/index.php?rid=4616847&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq6n5426t0860v286%2F In this report, we show the antiproliferative activity of withaphysalin F and its effect in arresting cells in the G2/M phase of the cell cycle. These two effects are the result of the interference of withaphysalin F in the polymerization of microtubules. Withaphysalin F also induced DNA fragmentation, which can be related to an increase in mitochondrial membrane depolarization. These results suggest that interference of withaphysalin F in microtubule polymerization may induce cell cycle arrest in the G2/M phase and therefore contribute to growth inhibition of tumor cells in vitro. Taken together, these studies indicate that withaphysalin F could potentially be used as an anticancer drug. Content Type Journal ArticlePages 1-8DOI 10.1007/s10637-011-9649-xAuthors Danilo D. Rocha,... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4616847 Thu, 17 Mar 2011 18:33:12 +0100 4616847 http://www.medworm.com/index.php?rid=4601670&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F81lnn5hgj7265260%2F Conclusions Erlotinib, gemcitabine and capecitabine combination showed promising efficacy and good tolerability in metastatic PC. This efficacy was observed irrespective of K-RAS mutation, and EGFR expression was poor prognostic factor for OS. Content Type Journal ArticlePages 1-11DOI 10.1007/s10637-011-9651-3Authors Do-Youn Oh, Department of Internal Medicine, Seoul National University Hospital, 28 Yongondong, Chongno-gu, Seoul, 110-744 KoreaKeun Wook Lee, Seoul National University Bundang Hospital, Seongnam, South KoreaKyung-Hee Lee, Yeoungnam UH, Daegu, South KoreaChang-Hak Sohn, Pusan Paik H, Pusan, South KoreaYoung Suk Park, Samsung Medical Center, Seoul, South KoreaDae Young Zang, Hallym University Sacred Heart Hospital, Chuncheon, South KoreaHun-Mo Ryoo, Daegu Catholic Unive... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4601670 Mon, 14 Mar 2011 16:55:42 +0100 4601670 http://www.medworm.com/index.php?rid=4601671&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff7p64556p4518655%2F Conclusions Vandetanib at doses of 100 mg and 300 mg daily in combination with capecitabine and oxaliplatin was well tolerated. However, the addition of bevacizumab resulted in severe diarrhea in three out of four patients. Bevacizumab was not well tolerated with vandetanib and XELOX in combination. Content Type Journal ArticlePages 1-6DOI 10.1007/s10637-011-9656-yAuthors Elwyn C. Cabebe, Department of Medicine (Oncology), Stanford University School of Medicine, Stanford, CA USAGeorge A. Fisher, Department of Medicine (Oncology), Stanford University School of Medicine, Stanford, CA USABranimir I. Sikic, Department of Medicine (Oncology), Stanford University School of Medicine, Stanford, CA USA Journal Investigational New DrugsOnline ISSN 1573-0646Print ISSN 0167-6... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4601671 Mon, 14 Mar 2011 16:55:41 +0100 4601671 http://www.medworm.com/index.php?rid=4581856&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg3691k5l72m02352%2F Conclusion Saracatinib has insufficient activity as a single agent in patients with advanced gastric adenocarcinoma to warrant further investigation. Further development in gastric cancer would require rational drug combinations or identification of a tumor phenotype sensitive to Src inhibition. Content Type Journal ArticlePages 1-6DOI 10.1007/s10637-011-9650-4Authors Helen J. Mackay, Department of Medical Oncology, Princess Margaret Hospital, University of Toronto, Ontario, CanadaHeather J. Au, Cross Cancer Institute, University of Alberta, Edmonton, AB CanadaElaine McWhirter, Juravinski Cancer Centre, Hamilton, ON CanadaThierry Alcindor, McGill University Health Centre, Montreal, QC CanadaAndrea Jarvi, Department of Medical Oncology, Princess Margaret Hospital, Drug Development ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4581856 Fri, 11 Mar 2011 18:07:26 +0100 4581856 http://www.medworm.com/index.php?rid=4578495&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj567158246384733%2F Summary  Pazopanib is a novel multikinase inhibitor that shares a similar spectrum of target receptors with sorafenib and sunitinib. We have performed a systematic analysis to investigate the risk of HFSR to pazopanib and compare the difference in incidence between sorafenib, sunitinib, and pazopanib. Relevant studies were identified from PubMed (1998–2010) and abstracts presented at the American Society of Clinical Oncology Conferences between 2004 and 2010. Eligible studies were limited to prospective Phase II-III clinical trials in which cancer patients were treated with pazopanib 800 mg orally once daily. Incidence, relative risk (RR), and 95% confidence intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of included ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4578495 Thu, 10 Mar 2011 17:12:43 +0100 4578495 http://www.medworm.com/index.php?rid=4567144&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd8x16wm334628179%2F Summary  The pyrrolobenzodiazepines (PBDs) are naturally occurring antitumor antibiotics and a PBD dimer (SJG-136, SG2000) is in Phase II trials. SG2000 is a propyldioxy linked PBD dimer which binds sequence selectively in the minor groove of DNA forming DNA interstrand and intrastrand cross-linked adducts, and also mono-adducts depending on sequence. SG2057 is the corresponding dimer containing a pentyldioxy linkage. SG2057 has multilog differential in vitro cytotoxicity against a panel of human tumour cell lines with a mean GI50 of 212 pM. The agent is highly efficient at producing DNA interstrand cross-links in cells which form rapidly and persist over a 48 h period. Significant antitumor activity was demonstrated in several human tumor xenograft models. Cures were ob... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4567144 Mon, 07 Mar 2011 17:02:22 +0100 4567144 http://www.medworm.com/index.php?rid=4541567&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw65244508r762705%2F Conclusion Locoregional therapy with 5-fluorouracil encapsulated in PEGylated liposomes may further improve the treatment success with longer-lasting tumor regression and prolonged survival times. Content Type Journal ArticlePages 1-9DOI 10.1007/s10637-011-9646-0Authors Uwe Pohlen, Department of General, Vascular and Thoracic Surgery, Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin Hindenburgdamm 30, 12200 Berlin, GermanyHeinz J. Buhr, Department of General, Vascular and Thoracic Surgery, Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin Hindenburgdamm 30, 12200 Berlin, GermanyGerd Berger, Department of General, Vascular and Thoracic Surgery, Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin Hindenburgdamm 30, 12200 Berlin, Germa... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4541567 Mon, 28 Feb 2011 16:44:42 +0100 4541567 http://www.medworm.com/index.php?rid=4541568&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd212581t7983j65m%2F Summary  LY2457546 is a potent and orally bioavailable inhibitor of multiple receptor tyrosine kinases involved in angiogenic and tumorigenic signalling. In biochemical and cellular assays, LY2457546 demonstrates potent activity against targets that include VEGFR2 (KDR), PDGFRβ, FLT-3, Tie-2 and members of the Eph family of receptors. With activities against both Tie2 and Eph receptors, LY2457546 possesses an activity profile that distinguishes it from multikinase inhibitors. When compared head to head with sunitinib, LY2457546 was more potent for inhibition of endothelial tube formation in an in vitro angiogenesis co-culture model with an intermittent treatment design. In vivo, LY2457546 inhibited VEGF-driven autophosphorylation of lung KDR in the mouse and rat in a dose ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=4541568 Mon, 28 Feb 2011 16:44:41 +0100 4541568