Department of Oncology, The Sixth People's Hospital, Shanghai Jiao Tong University, No. 600, Yishan Road, Shanghai, 200233, China.
Lung. 2012 Oct;190(5):477-85. doi: 10.1007/s00408-012-9399-3. Epub 2012 Jun 19.
The aim of this study was to perform a systematic review and meta-analysis of all randomized controlled trials that compared the efficacy of doublet versus single third-generation cytotoxic agent as first-line treatment for elderly patients with advanced non-small-cell lung cancer (NSCLC).
Several databases including PubMed, Embase, and Cochrane databases were searched. The endpoints were overall survival (OS), time to progression (TTP), 1-year survival rate (1-year SR), overall response rate (ORR), and grade 3 or 4 adverse event (AE). We performed a meta-analysis of the randomized controlled trials using a fixed-effects model and an additional random-effects model when applicable. The results of the meta-analysis were expressed as hazard ratio (HR) or risk ratio (RR), with their corresponding 95 % confidence intervals (95 % CI). A subgroup meta-analysis was performed based on chemotherapy regimens.
Ten eligible trials involving 2,510 patients were identified. The intention-to-treatment (ITT) analysis demonstrated that doublet therapy was superior to single agent in terms of OS (HR = 0.84, 95 % CI = 0.71-1.00, p = 0.053), TTP (HR = 0.76, 95 % CI = 0.60-0.96, p = 0.022), 1-year SR (RR = 1.17, 95 % CI = 1.02-1.35, p = 0.03), and ORR (RR = 1.54, 95 % CI = 1.36-1.73, p = 0.000). Subgroup analysis also favored platinum-based doublet therapy in terms of 1-year SR (RR = 1.40, 95 % CI = 1.09-1.81, p = 0.009) and ORR (RR = 1.64, 95 % CI = 1.38-1.96, p = 0.000). Though gemcitabine-based doublet significantly increased ORR compared with single agent (RR = 1.45, 95 % CI = 1.23-1.71, p = 0.000), it did not translate into an increase in survival benefits. In addition, more incidences of grade 3 or 4 anemia, thrombocytopenia, and neurotoxicity were observed in the doublet combination group. With respect to grade 3 or 4 neutropenia and nonhematologic toxicities such as diarrhea, fatigue, nausea, and vomiting, equivalent frequencies were found between the two groups.
Our results indicated that doublet therapy was superior to a single third-generation cytotoxic agent for elderly patients with advanced NSCLC. The optimal dosage and schedule of platinum-based doublet should be investigated in future prospective clinical trials. Gemcitabine-based doublet could be considered for elderly patients who were not suitable for platinum-based chemotherapy.
本研究旨在对所有比较第三代细胞毒性药物双联方案与单药一线治疗老年晚期非小细胞肺癌（NSCLC）疗效的随机对照试验进行系统评价和荟萃分析。
检索了 PubMed、Embase 和 Cochrane 数据库等多个数据库。终点指标包括总生存期（OS）、无进展生存期（TTP）、1 年生存率（1 年 SR）、总缓解率（ORR）和 3 或 4 级不良事件（AE）。我们使用固定效应模型对随机对照试验进行了荟萃分析，并在适用时使用了额外的随机效应模型。荟萃分析的结果表示为风险比（HR）或风险比（RR），及其相应的 95%置信区间（95%CI）。根据化疗方案进行了亚组荟萃分析。
共纳入了 10 项符合条件的试验，涉及 2510 名患者。意向治疗（ITT）分析表明，与单药相比，双联治疗在 OS（HR=0.84，95%CI=0.71-1.00，p=0.053）、TTP（HR=0.76，95%CI=0.60-0.96，p=0.022）、1 年 SR（RR=1.17，95%CI=1.02-1.35，p=0.03）和 ORR（RR=1.54，95%CI=1.36-1.73，p=0.000）方面更具优势。亚组分析也倾向于铂类双联治疗在 1 年 SR（RR=1.40，95%CI=1.09-1.81，p=0.009）和 ORR（RR=1.64，95%CI=1.38-1.96，p=0.000）方面更具优势。虽然吉西他滨双联治疗与单药相比显著增加了 ORR（RR=1.45，95%CI=1.23-1.71，p=0.000），但并没有转化为生存获益的增加。此外，在双联治疗组中观察到更多的 3 或 4 级贫血、血小板减少和神经毒性。关于 3 或 4 级中性粒细胞减少症和腹泻、疲劳、恶心和呕吐等非血液学毒性等不良反应，两组的发生率相当。
我们的结果表明，与第三代单药细胞毒性药物相比，双联治疗对老年晚期 NSCLC 患者更具优势。未来的前瞻性临床试验应探讨铂类双联方案的最佳剂量和方案。对于不适合铂类化疗的老年患者，可以考虑使用吉西他滨双联治疗。
