Maximum-tolerated dose defined for single-agent gemcitabine: A phase I dose-escalation study in chemotherapy-naive patients with advanced non-small-cell lung cancer

Purpose: We conducted a phase I trial of the novel nucleoside analog, gemcitabine, in chemotherapy-naive patients with advanced non-small-cell sung cancer (NSCLC) to determine the maximum-tolerated dose and efficacy in this population, Patients and Methods: Eligibility requirements included stage III or IV NSCLC, performance status less than or equal to 1, and no prior chemotherapy. Gemcitabine was administered as a 30-minute intravenous infusion weekly for 3 weeks every 4 weeks. We enrolled patients at doses that ranged from 1,000 to 2,800 mg/m(2)/wk (three patients per cohort). Responses were assessed after every two courses (8 weeks). Results: We treated 33 chemotherapy-naive patients with stage III (n = 5) or IV (n = 28) NSCLC. Most herd performance status 1, and 67% had adenocarcinoma. Eight of 32 assessable patients (25%) achieved a partial response. The projected median survival duration (all patients) is 49 weeks. The maximum-tolerated dose was 2,200 mg/m(2)/wk for 3 weeks every 4 weeks; dose-limiting toxicity was myelosuppression and reversible transaminase elevation. Other side effects were consistently mild. The maximum dose-intensity achieved with the first two cycles was 2,362 mg/m(2)/wk for 3 weeks every 4 weeks, which is a feasible phase It starting dose. Conclusion: This study estimates a phase II starting dose of gemcitabine in chemotherapy-naive patients to be 2,400 mg/m(2)/wk for 3 consecutive weeks every 4 weeks; this is much higher than that previously reported in heavily pretreated patients. Twenty five percent of patients with advanced NSCLC achieved a partial response to gemcitabine. This significant activity in conjunction with a very favorable toxicity profile supports the further evaluation of gemcitabine in combination with other active agents. (C) 1997 by American Society of Clinical Oncology.