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

F. V. Fossella, S. M. Lippman, D. M. Shin, P. Tarassoff, M. Calayag-Jung, R. Perez-Soler, J. S. Lee, W. K. Murphy, B. Glisson, E. Rivera, W. K. Hong

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124 Scopus citations


Purpose: We conducted a phase I trial of the novel nucleoside analog, gemcitabine, in chemotherapy-naive patients with advanced non-small-cell lung 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 ≤ 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/m2/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 had 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/m2/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/m2/wk for 3 weeks every 4 weeks, which is a feasible phase II starting dose. Conclusion: This study estimates a phase II starting dose of gemcitabine in chemotherapy-naive patients to be 2,400 mg/m2/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.

Original languageEnglish (US)
Pages (from-to)310-316
Number of pages7
JournalJournal of Clinical Oncology
Issue number1
Publication statusPublished - Jan 1997
Externally publishedYes


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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