Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer

Joachim Von Pawel, Joan H. Schiller, Frances A. Shepherd, Scott Z. Fields, J. P. Kleisbauer, Nick G. Chrysson, David J. Stewart, Peter I. Clark, Martin C. Palmer, Alain Depierre, James Carmichael, Jacqueline B. Krebs, Graham Ross, Stephen R. Lane, Richard Gralla

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842 Scopus citations


Purpose: Topotecan and cyclophosphamide, doxorubicin, and vincristine (CAV) were evaluated in a randomized, multicenter study of patients with small-cell lung cancer (SCLC) who had relapsed at least 60 days after completion of first-line therapy. Patients and Methods: Patients received either topotecan (1.5 mg/m2) as a 30-minute infusion daily for 5 days every 21 days (n = 107) or CAV (cyclophosphamide 1,000 mg/m2, doxorubicin 45 mg/m2, and vincristine 2 mg) infused on day 1 every 21 days (n = 104). Eligibility included the following: bidimensionally measurable disease, Eastern Cooperative Oncology Group performance status of less than or equal to 2, and adequate marrow, liver, and renal function. Response was confirmed by blinded independent radiologic review. Results: Response rate was 26 of 107 patients (24.3%) treated with topotecan and 19 of 104 patients (18.3%) treated with CAV (P = .285). Median times to progression were 13.3 weeks (topotecan) and 12.3 weeks (CAV) (P = .552). Median survival was 25.0 weeks for topotecan and 24.7 weeks for CAV (P = .795). The proportion of patients who experienced symptom improvement was greater in the topotecan group than in the CAV group for four of eight symptoms evaluated, including dyspnea, anorexia, hoarseness, and fatigue, as well as interference with daily activity (P ≤ .043). Grade 4 neutropenia occurred in 37.8% of topotecan courses versus 51.4% of CAV courses (P < .001). Grade 4 thrombocytopenia and grade 3/4 anemia occurred more frequently with topotecan, occurring in 9.8% and 17.7% of topotecan courses versus 1.4% and 7.2% of CAV courses, respectively (P < .001 for both). Nonhematologic toxicities were generally grade 1 to 2 for both regimens. Conclusion: Topotecan was at least as effective as CAV in the treatment of patients with recurrent SCLC and resulted in improved control of several symptoms.

Original languageEnglish (US)
Pages (from-to)658-667
Number of pages10
JournalJournal of Clinical Oncology
Issue number2
StatePublished - Feb 1999
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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