Gemcitabine-based combinations for inoperable pancreatic cancer:: Have we made real progress?: A meta-analysis of 20 phase 3 trials
Gemcitabine-based combinations for inoperable pancreatic cancer:: Have we made real progress?: A meta-analysis of 20 phase 3 trials
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DOI：
10.1002/cncr.22809
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发表时间：
2007-08-01
期刊：
影响因子：
6.2
通讯作者：
Giannarelli, Diana
中科院分区：
文献类型：
--
作者：
Bria, Emilio;Milella, Michele;Giannarelli, Diana
背景资料。为了提高吉西他滨治疗晚期胰腺癌的疗效，已经进行了几次尝试，方法是将其与其他化疗或分子靶向药物相结合。然而，随机试验产生了相互矛盾的结果。所有比较单药吉西他滨和基于吉西他滨的联合用药的前瞻性、随机化、3期试验都被认为符合当前分析的条件。以文献为基础进行荟萃分析，通过固定效应模型方法和随机效应模型方法得出具有95%可信区间的基于事件的相对风险比，并以总生存期(OS)为主要终点。为了估计最终受益的程度，计算了绝对差异和1名患者需要治疗的患者数量(NNT)。根据联合应用吉西他滨的药物类型进行OS的敏感性分析。确定了涉及6296名患者的20项试验。在总体人群或敏感性分析中，没有观察到主要终点的显著差异。相反，在总体人群的无进展存活率(PFS)和总体应答率(ORR)方面都有明显的优势，绝对收益分别为2.6%(NTT 39例患者)和3.0%(NNT=33例患者)。与单药吉西他滨(分别为10%和6.5%)相比，铂类药物组合导致了最大的PFS和ORR的绝对好处，但这并没有导致OS的好处。PFS的改善而不是ORR的改善与OS的改善相关。单药吉西他滨仍然是晚期胰腺癌患者的标准治疗药物。然而，铂/吉西他滨联合用药似乎能改善PFS和ORR，因此，可以考虑在特定患者中使用。
Background. Several attempts have been made at improving the efficacy of gemcitabine in advanced pancreatic cancer by combining it with other chemotherapeutic or molecularly targeted agents. However, randomized trials have produced conflicting results.Methods. All prospective, randomized, phase 3 trials that compared single-agent gemcitabine with gemcitabine-based combinations were considered eligible for the current analysis. A literature- based meta-analysis was performed, event-based relative risk ratios with 95% confidence intervals were derived through both a fixed-effect model approach and a random-effect model approach, and overall survival (OS) was explored as the primary endpoint. To estimate the magnitude of the eventual benefit, absolute differences and the number of patients needed to treat (NNT) for 1 patient to benefit were calculated. A sensitivity analysis for OS was performed according to the type of agent used in combination with gemcitabine.Results. Twenty trials that involved 6296 patients were identified. No significant differences in the primary endpoint were observed in the overall population or in the sensitivity analysis. Conversely, a significant advantage was evident with regard to both progression- free survival (PFS) and the overall response rate (ORR) in the overall population, with an absolute benefit of 2.6% (NTT 39 patients) and 3.0% (NNT = 33 patients). Platinum combinations led to the greatest absolute benefits for PFS and ORR compared with single-agent gemcitabine (10% and 6.5%, respectively), but this did not result in an OS benefit. Improvement in PFS, but not in the ORR, was correlated with an improvement in OS.Conclusions. Single-agent gemcitabine remains the standard of care for patients with advanced pancreatic cancer. However, platinum/ gemcitabine combinations appeared to improve PFS and the ORR and, thus, may be considered in selected patients.