Optimal duration of first-line chemotherapy for advanced non-small cell lung cancer: A systematic review with meta-analysis

Background: The optimal duration of first-line chemotherapy for advanced non-small cell lung cancer (NSCLC) has been a matter for debate for nearly 20 years. In order to elucidate this issue, a meta-analysis comparing the different durations of same treatments was performed. Methods: We searched for all published randomised controlled trials (RCTs) comparing different durations of first-line treatment of advanced NSCLC. The MEDLINE, EMBASE, LILACS and CENTRAL databases were searched for RCTs comparing a defined number of cycles of chemotherapy versus continuing treatment until disease progression, or a defined number of cycles versus a higher number of cycles of the same chemotherapy. Trials including biological agents were excluded. Results: Seven trials that included 1559 patients were analysed. Treatment for more than 4 cycles was associated with a non-statistically significant decrease in the hazard of mortality relative to shorter treatment (hazard ratio (HR) = 0.97; 95% confidence interval (CI) = 0.84-1.11; P = .65). In those treated with third-generation chemotherapy through the whole study time, treatment for more than 4 cycles was associated with a non-statistically significant increase in mortality (HR = 1.08; 95% CI = 0.90-1.28; P = .28). Patients receiving more chemotherapy had significant longer progression-free survival (HR = .75; 95% CI = 0.60-0.85; P < 0.0001) than the group with shorter duration of treatment. In an intent-to-treat analysis, there was no difference in the overall response rate between the groups (odds ratio (OR) = 0.78; 95% CI = 0.60-1.01; P = .96). Longer treatment was associated with more severe leucopaenia but with no significant increase in non-haematological toxicities. Conclusions: In patients with advanced NSCLC the use of more than 4 cycles of first-line chemotherapy with third-generation regimens significantly increases progression-free survival but not overall survival and is associated with higher incidence of adverse events. There is no evidence to support continuous chemotherapy until progression in patients with lung cancer. (C) 2008 Elsevier Ltd. All rights reserved.45460160