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Hideki Kamada - One of the best experts on this subject based on the ideXlab platform.
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a randomized phase ii study of Gemcitabine and s 1 combination therapy versus Gemcitabine monotherapy for advanced biliary tract cancer
Cancer Chemotherapy and Pharmacology, 2013Co-Authors: Takashi Sasaki, Nobuo Toda, Hirofumi Kogure, Hiroyuki Isayama, Yousuke Nakai, Naoki Sasahira, Ichiro Yasuda, Keiji Hanada, Hiroyuki Maguchi, Hideki KamadaAbstract:Purpose In order to confirm the impact of adding S-1 to Gemcitabine, we conducted a randomized phase II study to compare the combination therapy of Gemcitabine plus S-1 to Gemcitabine monotherapy in patients with advanced biliary tract cancer.
G. J. Peters - One of the best experts on this subject based on the ideXlab platform.
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Pharmacology of the paclitaxel–cisplatin, Gemcitabine–cisplatin, and paclitaxel–Gemcitabine combinations in patients with advanced non-small cell lung cancer
Cancer Chemotherapy and Pharmacology, 2006Co-Authors: J. R. Kroep, E. F. Smit, G. Giaccone, K. Born, J. H. Beijnen, C. J. Groeningen, W. J. F. Vijgh, P. E. Postmus, H. M. Pinedo, G. J. PetersAbstract:Purpose : To compare the pharmacology of the paclitaxel–cisplatin, Gemcitabine–cisplatin and paclitaxel–Gemcitabine combinations in patients with advanced non-small cell lung cancer (NSCLC). Patients and methods : Twenty-four chemo-naive patients with advanced NSCLC were randomized to receive one of the three regimens. Plasma pharmacokinetics and pharmacologic parameters in mononuclear cells were compared and related to toxicity and efficacy. Results : Pharmacological parameters of Gemcitabine and cisplatin were not influenced by the combination with one of the other agents, while the paclitaxel clearance was significantly lower for the combination with cisplatin as compared to Gemcitabine ( P =0.024). The percentage decrease in platelets was significantly higher for the Gemcitabine combinations ( P =0.004) and related to the dFdCTP-C_max ( P =0.030). Pharmacologic parameters were not related to response or survival. Conclusions : Gemcitabine and cisplatin pharmacology were not influenced by the combination with one of the other agents, while paclitaxel has a lower clearance in combination with cisplatin as compared to Gemcitabine.
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Combination chemotherapy studies with Gemcitabine.
Seminars in oncology, 1997Co-Authors: C J Van Moorsel, P. E. Postmus, G Veerman, A M Bergman, A Guechev, J B Vermorken, G. J. PetersAbstract:Gemcitabine (2',2'-difluorodeoxycytidine) is an antineoplastic agent with clinical activity against ovarian carcinoma, small cell and non-small cell lung cancers, head and neck cancer, bladder cancer, breast cancer, and pancreatic cancer. Cisplatin (CDDP), etoposide (VP-16), and mitomycin C (MMC) are well-known anticancer agents that are also active against many of these types of cancer. Because of the low toxicity profile of Gemcitabine and the differences in mechanism of cytotoxicity, combinations of these drugs with Gemcitabine were studied in vitro and in vivo. Cells were exposed in vitro for 1, 4, 24, or 72 hours to Gemcitabine in combination with these drugs, either simultaneously or sequentially in a constant ratio. Another approach consisted of exposure to a combination of the approximate IC25 of one drug and varying concentrations of the other drug. Synergism for several of these combinations was found in the human ovarian cancer cell line A2780, its CDDP-resistant variant ADDP, its Gemcitabine-resistant variant AG6000, and in the non-small cell lung cancer cell lines H322 and Lewis lung (LL) after a 72-hour drug treatment. Studies of the possible mechanisms of action initially focused on the major metabolic features of each drug. CDDP did not enhance the accumulation of Gemcitabine triphosphate and caused only marginal changes in the extent of DNA double-strand breaks (DSBs) induced by Gemcitabine in these cell lines. Gemcitabine increased platinum accumulation only in the ADDP cell line, but the DNA platination was enhanced in the A2780, ADDP, AG6000, and LL cell lines. MMC did not influence the formation of DSBs by Gemcitabine in the LL cell line. The combination of VP-16 and Gemcitabine, however, resulted in the formation of more DSBs in this cell line than each drug alone. This effect was even more pronounced when cells were exposed to VP-16 4 hours before Gemcitabine. In vivo, the antitumor activity of a combination of 50 mg/kg Gemcitabine and 6 mg/kg CDDP was more effective against LL tumors than each compound alone. In conclusion, Gemcitabine is an attractive drug to combine with a wide range of anticancer drugs; synergism is often schedule dependent.
Takashi Sasaki - One of the best experts on this subject based on the ideXlab platform.
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a randomized phase ii study of Gemcitabine and s 1 combination therapy versus Gemcitabine monotherapy for advanced biliary tract cancer
Cancer Chemotherapy and Pharmacology, 2013Co-Authors: Takashi Sasaki, Nobuo Toda, Hirofumi Kogure, Hiroyuki Isayama, Yousuke Nakai, Naoki Sasahira, Ichiro Yasuda, Keiji Hanada, Hiroyuki Maguchi, Hideki KamadaAbstract:Purpose In order to confirm the impact of adding S-1 to Gemcitabine, we conducted a randomized phase II study to compare the combination therapy of Gemcitabine plus S-1 to Gemcitabine monotherapy in patients with advanced biliary tract cancer.
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feasibility study of Gemcitabine and cisplatin combination chemotherapy for patients with refractory biliary tract cancer
Investigational New Drugs, 2011Co-Authors: Takashi Sasaki, Hirofumi Kogure, Hiroyuki Isayama, Yousuke Nakai, Suguru Mizuno, Keisuke Yamamoto, Hiroshi Yagioka, Yoko Yashima, Kazumichi Kawakubo, Osamu TogawaAbstract:Gemcitabine and cisplatin combination chemotherapy have been shown to have promising efficacy for the treatment of advanced biliary tract cancer (BTC) as a first-line chemotherapy. However, this treatment has not been approved for clinical practice in Japan. Oral fluoropyrimidines (e.g., S-1 and capecitabine) are also promising agents that are widely used with or without Gemcitabine. Unfortunately, there is no standard chemotherapy for patients refractory to Gemcitabine and oral fluoropyrimidine. We conducted a feasibility study of Gemcitabine and cisplatin combination chemotherapy for patients with advanced BTC who are refractory to Gemcitabine and S-1. Gemcitabine (1,000 mg/m2) and cisplatin (25 mg/m2) were administered intravenously on days 1 and 8, and this regimen was repeated every 3 weeks. Tumor response was assessed every two cycles using the Response Evaluation Criteria in Solid Tumors version 1.0. Twenty patients with pathologically confirmed BTC were enrolled. Gemcitabine and cisplatin combination chemotherapy was administered as a second-line chemotherapy in thirteen patients and as a third-line chemotherapy in seven patients. Tumor response did not occur in any of the cases. Fourteen patients demonstrated stable diseases, and the disease control rate was 70%. Median overall survival and time-to-progression were 5.9 months (95% CI, 3.9–11.3 months) and 3.6 months (95% CI, 2.2–4.2 months), respectively. Grade 3/4 toxicities included leucopenia (35%), neutropenia (35%), anemia (20%), and thrombocytopenia (15%). Two patients treated for approximately 1 year developed cisplatin-related toxicities. In conclusion, Gemcitabine and cisplatin combination chemotherapy produces a limited tumor response in BTC, but may prolong patient’s survival.
Mirella Sannicolo - One of the best experts on this subject based on the ideXlab platform.
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randomized phase iii trial of Gemcitabine plus cisplatin compared with single agent Gemcitabine as first line treatment of patients with advanced pancreatic cancer the gip 1 study
Journal of Clinical Oncology, 2010Co-Authors: G Colucci, Roberto Labianca, Francesco Di Costanzo, Vittorio Gebbia, Giacomo Carteni, B Massidda, Elisa Dapretto, Luigi Manzione, E Piazza, Mirella SannicoloAbstract:Purpose Single-agent Gemcitabine became standard first-line treatment for advanced pancreatic cancer after demonstration of superiority compared with fluorouracil. The Gruppo Italiano Pancreas 1 randomized phase III trial aimed to compare Gemcitabine plus cisplatin versus Gemcitabine alone (ClinicalTrials.gov ID NCT00813696). Patients and Methods Patients with locally advanced or metastatic pancreatic cancer, age 18 to 75 years, and Karnofsky performance status (KPS) ≥ 50, were randomly assigned to receive Gemcitabine (arm A) or Gemcitabine plus cisplatin (arm B). Arm A: Gemcitabine 1,000 mg/m2 weekly for 7 weeks, and, after a 1-week rest, on days 1, 8, and 15 every 4 weeks. Arm B: cisplatin 25 mg/m2 added weekly to Gemcitabine, except cycle 1 day 22. Primary end point was overall survival. To have 8% power of detecting a 0.74 hazard ratio (HR) of death, with bilateral α .05, 355 events were needed and 400 patients planned. Results Four hundred patients were enrolled (arm A: 199; arm B: 201). Median age w...
David Goldstein - One of the best experts on this subject based on the ideXlab platform.
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nab paclitaxel plus Gemcitabine for metastatic pancreatic cancer long term survival from a phase iii trial
Journal of the National Cancer Institute, 2015Co-Authors: David Goldstein, Werner Scheithauer, Robert Hassan Elmaraghi, Pascal Hammel, Volker Heinemann, Volker Kunzmann, J Sastre, Salvatore Siena, Josep Tabernero, Luis TeixeiraAbstract:Background Positive findings from the phase III MPACT trial led to the regulatory approval of nab-paclitaxel plus Gemcitabine as a treatment option for patients with metastatic pancreatic cancer. This report is an update of overall survival (OS) based on longer follow-up. Methods Patients (n = 861) with metastatic pancreatic cancer and a Karnofsky performance status of 70 or greater were randomly assigned one to one to receive nab-paclitaxel + Gemcitabine or Gemcitabine alone. Efficacy data for this post hoc analysis were collected through May 9, 2013. Exploratory analyses of carbohydrate antigen 19-9 (CA19-9) and neutrophil-to-lymphocyte ratio (NLR) were conducted. The primary efficacy endpoint was OS, which was analyzed for all randomly assigned patients by the Kaplan-Meier method. All statistical tests were two-sided. Results The median OS was statistically significantly longer for nab-paclitaxel plus Gemcitabine vs Gemcitabine alone (8.7 vs 6.6 months, hazard ratio [HR] = 0.72, 95% confidence interval [CI] = 0.62 to 0.83, P three-year) survivors were identified in the nab-paclitaxel plus Gemcitabine arm only (4%). In pooled treatment arm analyses, higher CA19-9 level and NLR at baseline were statistically significantly associated with worse OS. There appeared to be a treatment effect for OS favoring nab-paclitaxel plus Gemcitabine over Gemcitabine alone in poor-prognosis subgroups defined by these factors (HR = 0.612, P 5). Conclusions These data confirm and extend the primary report of OS, supporting the superior efficacy of nab-paclitaxel plus Gemcitabine over Gemcitabine alone. Subgroup analyses support the relevance of CA 19-9 and NLR as prognostic markers in metastatic pancreatic cancer.
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erlotinib plus Gemcitabine compared with Gemcitabine alone in patients with advanced pancreatic cancer a phase iii trial of the national cancer institute of canada clinical trials group
Journal of Clinical Oncology, 2007Co-Authors: Malcolm J Moore, David Goldstein, John T Hamm, A Figer, J R Hecht, Steven Gallinger, Heather J Au, Pawel Murawa, David Walde, Robert A WolffAbstract:Purpose Patients with advanced pancreatic cancer have a poor prognosis and there have been no improvements in survival since the introduction of Gemcitabine in 1996. Pancreatic tumors often overexpress human epidermal growth factor receptor type 1 (HER1/EGFR) and this is associated with a worse prognosis. We studied the effects of adding the HER1/EGFR-targeted agent erlotinib to Gemcitabine in patients with unresectable, locally advanced, or metastatic pancreatic cancer. Patients and Methods Patients were randomly assigned 1:1 to receive standard Gemcitabine plus erlotinib (100 or 150 mg/d orally) or Gemcitabine plus placebo in a double-blind, international phase III trial. The primary end point was overall survival. Results A total of 569 patients were randomly assigned. Overall survival based on an intent-to-treat analysis was significantly prolonged on the erlotinib/Gemcitabine arm with a hazard ratio (HR) of 0.82 (95% CI, 0.69 to 0.99; P .038, adjusted for stratification factors; median 6.24 months v 5.91 months). One-year survival was also greater with erlotinib plus Gemcitabine (23% v 17%; P .023). Progression-free survival was significantly longer with erlotinib plus Gemcitabine with an estimated HR of 0.77 (95% CI, 0.64 to 0.92; P .004). Objective response rates were not significantly different between the arms, although more patients on erlotinib had disease stabilization. There was a higher incidence of some adverse events with erlotinib plus Gemcitabine, but most were grade 1 or 2.
