Bria Emilio, Milella Michele, Gelibter Alain, Cuppone Federica, Pino Maria Simona, Ruggeri Enzo Maria, Carlini Paolo, Nisticò Cecilia, Terzoli Edmondo, Cognetti Francesco, Giannarelli Diana
Department of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy.
Cancer. 2007 Aug 1;110(3):525-33. doi: 10.1002/cncr.22809.
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.
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.
Twenty trials that involved 6,296 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.
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.
人们曾多次尝试通过将吉西他滨与其他化疗药物或分子靶向药物联合使用来提高其在晚期胰腺癌中的疗效。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与基于吉西他滨的联合用药的前瞻性、随机、3期试验均被认为符合当前分析的条件。进行了基于文献的荟萃分析，通过固定效应模型方法和随机效应模型方法得出了具有95%置信区间的基于事件的相对风险比，并将总生存期（OS）作为主要终点进行探讨。为了估计最终获益的程度，计算了绝对差异和为使1例患者获益所需治疗的患者数量（NNT）。根据与吉西他滨联合使用的药物类型对OS进行了敏感性分析。
共纳入了涉及6296例患者的20项试验。在总体人群或敏感性分析中，未观察到主要终点有显著差异。相反，在总体人群中，无进展生存期（PFS）和总缓解率（ORR）均有显著优势，绝对获益分别为2.6%（NNT = 39例患者）和3.0%（NNT = 33例患者）。与单药吉西他滨相比，铂类联合用药在PFS和ORR方面带来的绝对获益最大（分别为10%和6.5%），但未带来OS获益。PFS的改善与OS的改善相关，但ORR的改善与OS的改善无关。
单药吉西他滨仍然是晚期胰腺癌患者的标准治疗方案。然而，铂类/吉西他滨联合用药似乎可改善PFS和ORR，因此，可在特定患者中考虑使用。
