A three-arm phase III randomised trial comparing combinations of platinum derivatives, ifosfamide and/or gemcitabine in stage IV non-small-cell lung cancer.

OBJECTIVE: To determine, in stage IV non-small-cell lung cancer (NSCLC), if the combination of gemcitabine-a new active drug-with ifosfamide (IG) or with the cisplatin-carboplatin association (CCG) will improve survival (primary end point) in comparison with a first-generation regimen, cisplatin-carboplatin-ifosfamide (CCI). PATIENTS AND METHODS: A total of 284 chemotherapy-na?ve patients with metastatic NSCLC were randomised. Four were ineligible and 16 were not assessable for responses. Cisplatin was given at 60 mg/m2 on day 1, carboplatin AUC 3 mg.min/ml on day 1, ifosfamide 4.5 g/m2 on day 1 and gemcitabine 1 g/m2 on days 1, 8 and 15. Courses were repeated every 4 weeks. Response was assessed after three courses and chemotherapy was continued in responding patients until best response. There were 94 eligible patients in the CCI arm, 92 in CCG and 94 in the IG arm. RESULTS: The objective response rates for CCI, CCG and IG were 23% [95% confidence interval (CI) 15% to 32%], 29% (95% CI 20% to 39%) and 25% (95% CI 16% to 33%), respectively ( P = 0.61). Median survival time was 24, 34 and 30 weeks, respectively (P = 0.20). One-year survival was 23, 33 and 35%, and 2-year survival was 11, 14 and 17%, respectively. In some subgroups (older patients, women), there was a significant survival advantage for CCG and IG compared with CCI. Toxicity was tolerable: severe alopecia was less frequent in the CCG arm, and IG was associated with significantly more thrombopenia while CCG was associated with more leucopenia. CONCLUSION: In stage IV NSCLC, treatment with regimens including the new drug gemcitabine were associated with a better but not statistically significant observed survival compared with a classical first-generation cisplatin-containing regimen. The non-platinum combination of gemcitabine was as effective as its combination with platinum.