Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer
Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer
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DOI：
10.1200/jco.2004.10.112
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发表时间：
2004-04-15
影响因子：
45.3
通讯作者：
Von Hoff, D
中科院分区：
文献类型：
--
作者：
Van Cutsem, E;de Velde, HV;Von Hoff, D
目的：确定在标准吉西他滨治疗中添加法尼基转移酶抑制剂替匹法尼（Zarnestra，R115777；比利时贝尔瑟的强生制药研发公司）是否能提高晚期胰腺癌的总体生存率。
患者与方法：这项随机、双盲、安慰剂对照研究比较了吉西他滨 + 替匹法尼与吉西他滨 + 安慰剂在先前未接受过系统治疗的晚期胰腺腺癌患者中的疗效。替匹法尼以200mg每日两次口服持续给药；吉西他滨以1000mg/m²静脉注射，每周1次，连续7周，然后每4周每周1次，连续3周。主要终点是总体生存率；次要终点包括6个月和1年生存率、无进展生存期、缓解率、安全性和生活质量。
结果：688名患者入组。两个治疗组之间的基线特征均衡良好。在生存参数方面未观察到有统计学意义的差异。试验组的中位总体生存期为193天，对照组为182天（P = 0.75）；6个月和1年生存率在试验组分别为53%和27%，对照组分别为49%和24%；中位无进展生存期在试验组为112天，对照组为109天。试验组报告有10例与药物相关的死亡，对照组有7例。试验组中性粒细胞减少和血小板减少≥3级的发生率分别为40%和15%，对照组分别为30%和12%。两组非血液学不良事件的发生率相似。
结论：与单药吉西他滨相比，吉西他滨和替匹法尼联合使用具有可接受的毒性特征，但不能延长晚期胰腺癌的总体生存期。（C）2004年美国临床肿瘤学会
Purpose To determine whether addition of the farnesyltransferase inhibitor tipifarnib (Zarnestra, R115777; Johnson and Johnson Pharmaceutical Research and Development, Beerse, Belgium) to standard gemcitabine therapy improves overall survival in advanced pancreatic cancer.Patients and Methods This randomized, double-blind, placebo-controlled study compared gemcitabine + tipifarnib versus gemcitabine + placebo in patients with advanced pancreatic adenocarcinoma previously untreated with systemic therapy. Tipifarnib was given at 200 mg bid orally continuously; gemcitabine was given at 1,000 mg/m(2) intravenously weekly X 7 for 8 weeks, then weekly X 3 every 4 weeks. The primary end point was overall survival; secondary end points included 6-month and 1-year survival rates, progression-free survival, response rate, safety, and quality of life.Results Six hundred eighty-eight patients were enrolled. Baseline characteristics were well balanced between the two treatment arms. No statistically significant differences in survival parameters were observed. The median overall survival for the experimental arm was 193 v 182 days for the control arm (P = .75); 6-month and 1-year survival rates were 53% and 27% v 49% and 24% for the control arm, respectively; median progression-free survival was 112 v 109 days for the control arm. Ten drug-related deaths were reported for the experimental arm and seven for the control arm. Neutropenia and thrombocytopenia grade greater than or equal to 3 were observed in 40% and 15% in the experimental arm versus 30% and 12% in the control arm. Incidences of nonhematologic adverse events were similar in two groups.Conclusion The combination of gemcitabine and tipifarnib has an acceptable toxicity profile but does not prolong overall survival in advanced pancreatic cancer compared with single-agent gemcitabine. (C) 2004 by American Society of Clinical Oncology.