Delbaldo Catherine, Michiels Stefan, Syz Nathalie, Soria Jean-Charles, Le Chevalier Thierry, Pignon Jean-Pierre
Department of Medecine, Institut Gustave-Roussy, Villejuif Cedex, France.
JAMA. 2004 Jul 28;292(4):470-84. doi: 10.1001/jama.292.4.470.
Randomized trials have demonstrated that adding a drug to a single-agent or to a 2-agent regimen increased the tumor response rate in patients with advanced non-small-cell lung cancer (NSCLC), although its impact on survival remains controversial.
To evaluate the clinical benefit of adding a drug to a single-agent or 2-agent chemotherapy regimen in terms of tumor response rate, survival, and toxicity in patients with advanced NSCLC.
Data from all randomized controlled trials performed between 1980 and 2001 (published between January 1980 and October 2003) comparing a doublet regimen with a single-agent regimen or comparing a triplet regimen with a doublet regimen in patients with advanced NSCLC. There were no language restrictions. Searches of MEDLINE and EMBASE were performed using the search terms non-small-cell lung carcinoma/drug therapy, adenocarcinoma, large-cell carcinoma, squamous-cell carcinoma, lung, neoplasms, clinical trial phase III, and randomized trial. Manual searches were also performed to find conference proceedings published between January 1982 and October 2003.
Two independent investigators reviewed the publications and extracted the data. Pooled odds ratios (ORs) for the objective tumor response rate, 1-year survival rate, and toxicity rate were calculated using the fixed-effect model. Pooled median ratios (MRs) for median survival also were calculated using the fixed-effect model. ORs and MRs lower than unity (<1.0) indicate a benefit of a doublet regimen compared with a single-agent regimen (or a triplet regimen compared with a doublet regimen).
Sixty-five trials (13 601 patients) were eligible. In the trials comparing a doublet regimen with a single-agent regimen, a significant increase was observed in tumor response (OR, 0.42; 95% confidence interval [CI], 0.37-0.47; P<.001) and 1-year survival (OR, 0.80; 95% CI, 0.70-0.91; P<.001) in favor of the doublet regimen. The median survival ratio was 0.83 (95% CI, 0.79-0.89; P<.001). An increase also was observed in the tumor response rate (OR, 0.66; 95% CI, 0.58-0.75; P<.001) in favor of the triplet regimen, but not for 1-year survival (OR, 1.01; 95% CI, 0.85-1.21; P =.88). The median survival ratio was 1.00 (95% CI, 0.94-1.06; P =.97).
Adding a second drug improved tumor response and survival rate. Adding a third drug had a weaker effect on tumor response and no effect on survival.
随机试验表明，在单药或两药方案基础上加用一种药物可提高晚期非小细胞肺癌（NSCLC）患者的肿瘤缓解率，但其对生存率的影响仍存在争议。
评估在晚期NSCLC患者中，在单药或两药化疗方案基础上加用一种药物在肿瘤缓解率、生存率和毒性方面的临床获益。
1980年至2001年期间（1980年1月至2003年10月发表）进行的所有随机对照试验的数据，这些试验比较了晚期NSCLC患者的双药方案与单药方案，或三药方案与双药方案。无语言限制。使用搜索词非小细胞肺癌/药物治疗、腺癌、大细胞癌、鳞状细胞癌、肺、肿瘤、III期临床试验和随机试验对MEDLINE和EMBASE进行检索。还进行了人工检索以查找1982年1月至2003年10月发表的会议论文集。
两名独立研究人员审查了这些出版物并提取了数据。使用固定效应模型计算客观肿瘤缓解率、1年生存率和毒性率的合并比值比（OR）。中位生存期的合并中位数比（MR）也使用固定效应模型计算。低于1.0（<1.0）的OR和MR表明双药方案优于单药方案（或三药方案优于双药方案）。
65项试验（13601例患者）符合条件。在比较双药方案与单药方案的试验中，观察到肿瘤缓解（OR，0.42；95%置信区间[CI]，0.37 - 0.47；P <.001）和1年生存率（OR，0.80；95% CI，0.70 - 0.91；P <.001）有显著提高，支持双药方案。中位生存比为0.83（95% CI，0.79 - 0.89；P <.001）。三药方案的肿瘤缓解率也有所提高（OR，0.66；95% CI，0.58 - 0.75；P <.001），但1年生存率未提高（OR，1.01；95% CI，0.85 - 1.21；P =.88）。中位生存比为1.00（95% CI，0.94 - 1.06；P =.97）。
加用第二种药物可改善肿瘤缓解率和生存率。加用第三种药物对肿瘤缓解的作用较弱，对生存率无影响。
