Randomized phase II trial of single-agent amrubicin or topotecan as second-line treatment in patients with small-cell lung cancer sensitive to first-line platinum-based chemotherapy

J Clin Oncol. 2011 Jan 20;29(3):287-93. doi: 10.1200/JCO.2010.29.8851. Epub 2010 Dec 6.

Abstract

Purpose: This phase II study evaluated the safety and efficacy of single-agent amrubicin versus topotecan in patients with small-cell lung cancer (SCLC) sensitive to first-line platinum-based chemotherapy.

Patients and methods: Patients were randomly assigned 2:1 to amrubicin (40 mg/m(2)/d in a 5-minute intravenous [IV] infusion, days 1 through 3, every 21 days) or topotecan (1.5 mg/m(2)/d in a 30-minute IV infusion, days 1 through 5, every 21 days). The primary efficacy end point was overall response rate (ORR) for amrubicin. Secondary end points included time to progression, median progression-free survival (PFS), and median overall survival (OS).

Results: Of 76 patients enrolled, 50 patients were randomly assigned to amrubicin, and 26 patients were randomly assigned to topotecan. Amrubicin treatment resulted in a significantly higher ORR than topotecan (44% v 15%; P = .021). Median PFS and median OS were 4.5 months and 9.2 months with amrubicin and 3.3 months and 7.6 months with topotecan, respectively. Tolerability was similar with both agents. However, grade 3 or worse neutropenia and thrombocytopenia seemed to be more frequent in the topotecan group as compared with the amrubicin group (78% and 61% v 61% and 39%, respectively).

Conclusion: Amrubicin shows promising activity, with an ORR of 44% compared with an ORR of 15% for topotecan as second-line treatment in patients with SCLC sensitive to first-line platinum-based chemotherapy. In addition, the safety profiles were comparable; however, a trend was noted for more frequent grade 3 or worse neutropenia and thrombocytopenia in the topotecan group as compared with the amrubicin group. Additional studies are ongoing.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anthracyclines / adverse effects
  • Anthracyclines / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Humans
  • Intention to Treat Analysis
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Small Cell Lung Carcinoma / drug therapy*
  • Survival Analysis
  • Thrombocytopenia / chemically induced
  • Topoisomerase I Inhibitors / adverse effects
  • Topoisomerase I Inhibitors / therapeutic use*
  • Topotecan / adverse effects
  • Topotecan / therapeutic use*
  • United States

Substances

  • Anthracyclines
  • Antineoplastic Agents
  • Topoisomerase I Inhibitors
  • Topotecan
  • amrubicin