Purpose: To compare the survival benefit obtained with cisplatin plus gemcitabine, a cisplatin-based triplet, and nonplatinum sequential doublets in advanced non–small-cell lung cancer (NSCLC).

Patients and Methods: Stage IIIB to IV NSCLC patients were randomly assigned to receive cisplatin 100 mg/m² day 1 plus gemcitabine 1,250 mg/m² days 1 and 8, every 3 weeks for six cycles (CG); cisplatin 100 mg/m² day 1 plus gemcitabine 1,000 mg/m² and vinorelbine 25 mg/m² days 1 and 8, every 3 weeks for six cycles (CGV); or gemcitabine 1,000 mg/m² plus vinorelbine 30 mg/m² days 1 and 8, every 3 weeks for three cycles, followed by vinorelbine 30 mg/m² days 1 and 8 plus ifosfamide 3 g/m² day 1, every 3 weeks for three cycles (GV–VI).

Results: Five hundred fifty-seven patients were assigned to treatment (182 CG, 188 CGV, 187 GV–VI). Response rates were significantly inferior for the nonplatinum sequential doublet (CG, 42%; CGV, 41%; GV–VI, 27%; CG v GV–VI, P = .003). No differences in median survival or time to progression were observed. Toxicity was higher for the triplet: grade 3 to 4 neutropenia (GC, 32%; CGV, 57%; GV–VI, 27%; P < .05); neutropenic fever (CG, 4%; CGV, 19%; GV–VI, 5%; P < .0001); grade 3 to 4 thrombocytopenia (CG, 19%; CGV, 23%; GV–VI, 3%; P = .0001); and grade 3 to 4 emesis (GC, 22%; GCV, 32%; GV–VI, 6%; P < .0001).

Conclusion: On the basis of these results, CG remains a standard regimen for first-line treatment of advanced NSCLC.