Docetaxel/gemcitabine or cisplatin/gemcitabine followed by docetaxel in the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC):: results of a multicentre randomized phase II trial

Background Most patients (pts) with metastatic non-small cell lung cancer (NSCLC) receive either single agents or chemotherapy doublets. Recent studies have demonstrated that triple-agent therapies may improve the response rate, but are associated with significant toxicity, and frequently do not prolong survival. A sequential triple-agent schedule may combine acceptable tolerability and good efficacy. We therefore conducted a multicentre, prospectively randomized study that evaluates a sequential three-drug schedule and a platinum-free doublet regimen. Patients and methods The pts with union international contre le cancer (UICC) stage IV NSCLC were randomized to one of two schedules: in arm Doc-Gem, they received gemcitabine (900 mg/m(2), 30 min infusion) on days 1 and 8, and docetaxel (75 mg/m(2), 1 h infusion) on day 1, repeated every 3 weeks up to six cycles. In arm Cis-Gem-->Doc, gemcitabine (900 mg/m(2), days 1 and 8) and cisplatin (70 mg/m(2), 1 h infusion, day 1) were given for three cycles, followed by three cycles of docetaxel (100 mg/m(2), day 1, repeated every 3 weeks). Results One hundred and thirteen pts were randomized to arms Doc-Gem (55 pts) and Cis-Gem-->Doc (58 pts). With Doc-Gem, 20.4% of pts responded to the treatment whereas 31.0% responded in arm Cis-Gem-->Doc (overall response, intent-to-treat, difference not significant). The median time to progression was 3.6 months in arm Doc-Gem [95% confidence interval (CI) 1.4, 5.9] and 5.2 months in arm Cis-Gem-->Doc (95% CI 3.1, 7.3). The median survival was 8.7 months with treatment Doc-Gem (95% CI 5.7, 11.6) and 9.4 months with treatment Cis-Gem-->Doc (95% CI 7.8, 11.0). The 1-year survival rates were 34 and 35%, respectively. Mild to moderate leukopenia was frequently seen with both schedules. Other common adverse events (AE) were nausea/vomiting, thrombocytopenia, anaemia, diarrhoea, and infections. No significant differences in AEs were observed between the schedules except for nausea/vomiting, which occurred more frequently with Cis-Gem-->Doc. Conclusion The sequential therapy comprising cisplatin, gemcitabine, and docetaxel demonstrated promising tumour control whereas the platinum-free combination (docetaxel/gemcitabine) was very well tolerated. However, the schedules resulted in comparable survival to recent large trials in pts with advanced NSCLC. The present results do not justify further phase III investigation.