Hematologic safety and tolerability of topotecan in recurrent ovarian cancer and small cell lung cancer: An integrated analysis

Deborah K. Armstrong, David Spriggs, Jeremey Levin, Ruth Poulin, Stephen Lane

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


The purpose was to conduct an integrated analysis of the cumulative hematologic toxicity of topotecan in patients with relapsed ovarian cancer and small cell lung cancer (SCLC). Data were pooled from eight phase II and phase III clinical studies performed in patients with relapsed stage III/IV ovarian cancer or extensive SCLC treated with topotecan at a dose of 1.5 mg/m 2 per day on days 1-5 of a 21-day course. Quantitative hematologic toxicities were assessed using the National Cancer Institute Common Toxicity Criteria. A total of 4,124 courses of therapy was administered to the 879 patients in the pooled population. Grade 4 neutropenia was experienced by 78% of patients. The lowest nadirs for neutrophils and platelets generally occurred after the first course of therapy, followed by improvement or stabilization in subsequent courses. Neutropenia was noncumulative. During the first course, significant risk factors were identified: renal impairment and advanced age (grade 3/4 thrombocytopenia and grade 4 neutropenia) and prior radiotherapy; performance status score ≥2; SCLC; and exposure to both cisplatin (Platinol®; Bristol-Myers Squibb, Princeton, NJ, http://www. bms.com) and carboplatin (Paraplatin®; Bristol-Myers Squibb) (grade 3/4 thrombocytopenia only). The most frequent interventions for hematologic toxicities were RBC transfusions, treatment delays, G-CSF support, and dose reductions. Analysis of neutrophil and platelet nadirs and dosing for each course of therapy showed no apparent evidence of cumulative neutropenia or thrombocytopenia. The risk of grade 3 or 4 anemia was higher during the first four courses of therapy and may need to be more aggressively managed with erythropoietin therapy.

Original languageEnglish (US)
Pages (from-to)686-694
Number of pages9
Issue number9
StatePublished - Oct 2005
Externally publishedYes


  • Myelosuppression
  • Neutropenia
  • Noncumulative
  • Ovarian cancer
  • Small cell lung cancer
  • Topotecan

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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