This study was designed to compare the outcome of stage IIIB/IV non-small cell lung cancer patients who were treated with chemotherapy but did not participate in clinical trials of first-line chemotherapy with patients that had been treated with three clinical trials during this period. From October 1997 through October 1999, 132 patients (stage IIIB, 31 patients; stage IV, 101 patients) who received at least one dose of chemotherapy but did not participate in first-line chemotherapy trials were included. Response was evaluated in 132 patients. Six (4.5%) achieved a complete response and 32 (24.3%) achieved a partial response, resulting in an overall response rate of 28.8% (95% CI, 21.0-36.6). The median overall survival for all 132 patients was 11 months (95% CI, 9.5-12.5), and the median progression-free survival was 4.2 months (95% CI, 3.4-5.0). The median overall and progression-free survival for patients (N=129) who participated in one of three clinical trials during the study period was 13.5 months (95% CI, 11.2-15.8) and 5.6 months (95% CI, 4.9-6.0), respectively. There was no significant difference in overall and progression-free survival between patients who did or did not participate in clinical trials (overall survival: P=0.36; progression-free survival: P=0.57). Our data suggest that the survival of patients who received chemotherapy but did not participate in clinical trials was similar to patients participated in clinical trials.