Randomized phase II study of daily versus continuous-infusion schedules of topotecan in the treatment of extensive-stage small cell lung cancers

Paul L. Schaefer, Randolph S. Marks, Michelle R. Mahoney, Jeff A. Sloan, Mitchell D. Bauman, Henry D. Tazelaar, John W. Kugler, James A. Mailliard, Larry P. Ebbert, Martin Wiesenfeld

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A randomized two-stage, phase II study was conducted to assess the antitumor activity of two different schedules of topotecan in the treatment of extensive-stage small-cell lung cancer (SCLC) in chemotherapy-naive patients. A total of 40 eligible patients were randomized to receive either the daily schedule, with topotecan being administered intravenously at 1.5 mg/m2 daily for 5 days every 3 weeks, or the continuousinfusion schedule, with topotecan administered intravenously at a dosage of 1.3 mg/m2 per day over 72 hours every 4 weeks. Randomization to the continuous-infusion schedule was discontinued due to inactivity, and an additional 20 patients were treated on the daily schedule. Patients received an average of 5 courses (range: 1-13) of the daily schedule compared to an average of 2 courses (range: 1-7) of the continuous-infusion schedule (p < 0.01). Confirmed response rates for the daily and continuous-infusion schedules are 62.5% (90% CI: 49-75%) and 15% (90% CI: 1-29%), respectively. Toxicity was predominantly hematologic with 92% (55/60) having greater than or equal to grade III neutropenia and 58% (35/60) reporting greater than or equal to grade III leukopenia for both IV schedules. Nonhematologic toxicity was very mild, with only 10% (6/60) patients experiencing grade IV toxicities. One patient died of infection on the continuous-infusion arm. Median times to progression for the daily and continuous-infusion schedules are 5 months (90% CI: 4.4-7.2) and 2 months (90% CI: 1.1-2.1), respectively. Estimated 1-year survival rates for patients receiving daily and continuous-infusion schedules are 63% (90% CI: 51-76%) and 55% (90% CI: 39-77%), respectively. Fifty percent (30/60) of patients received second-line therapy with etoposide and cisplatin. Forty-three percent (13/ 30) of patients who received second-line therapy achieved a confirmed response. Topotecan showed significant activity in the treatment of extensive stage SCLC when administered as a brief daily IV repeated every 3 weeks.

Original languageEnglish (US)
Pages (from-to)236-240
Number of pages5
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Issue number3
StatePublished - Jun 1 2003


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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