Single agent versus combination chemotherapy in patients with advanced nonsmall cell lung carcinoma: a meta-analysis of response, toxicity, and survival.

Abstract

This meta-analysis was conducted to compare the effects of single agent versus combination chemotherapy on response rate, toxicity, and survival of patients with advanced nonsmall cell lung carcinoma (NSCLC). The authors reviewed randomized clinical trials published in the medical literature and the reference lists of relevant articles. Objective response rate, survival at 6 and 12 months, and the incidence of treatment-related death were compared among all patients receiving single agent chemotherapy and those receiving combination chemotherapy. A subgroup analysis for all outcomes was conducted for 10 trials published between 1989 and 1996 that used a platinum analogue or vinorelbine as the single agent arm. The authors identified 38 potentially eligible trials, 25 of which (with a total of 5156 patients) were included in the meta-analysis. Overall, combination chemotherapy produced a nearly 2-fold increase in response rate compared with single agent chemotherapy (response rate [RR], 1.93; 95% confidence interval [CI], 1.54-2.42). However, combination chemotherapy also increased toxicity significantly, including a 3.6-fold increase in the risk of treatment-related death (RR, 3.5; 95% CI, 1.8-6.7). Survival at 6 months (RR, 1.10; 95% CI, 1.02-1.19) and 12 months (RR, 1.22; 95% CI, 1.03-1.45) was modestly superior with combination chemotherapy when all trials are included. However, when a platinum analogue or vinorelbine are used as single agents, this difference was no longer statistically significant at 6 months (RR, 1.03; 95% CI, 0.92-1.15) or at 12 months (RR, 1.10; 95% CI, 0.94-1.43). Combination chemotherapy increased objective response and toxicity rates compared with single-agent chemotherapy. Survival was prolonged only modestly with combination chemotherapy but not significantly so when more active single agents were used.