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

Purpose: Topotecan and cyclophosphamide, doxorubicin, and vincristine (CAV) were evaluated in a randomized, multicenter study of patients with small-c ell lung cancer (SCLC) who had relapsed at least 60 days after completion o f first-line therapy. Patients and Methods: Patients received either topotecan (1.5 mg/m(2)) as c t 30-minute infusion daily for 5 days every 21 days (n = 107) or CAV (cyclo phosphamide 1,000 mg/m(2), doxorubicin 45 mg/m(2), and vincristine 2 mg) in fused on day 1 every 21 days (n = 104). Eligibility included the following: bidimensionally measurable disease, Eastern Cooperative Oncology Group per formance status of less than or equal to 2, and adequate marrow, liver, and renal function. Response was confirmed by blinded independent radiologic r eview. Results: Response rate was 26 of 107 patients (24.3%) treated with topoteca n and 19 of 104 patients (18.3%) treated with CAV (P =.285), Median times t o progression were 13.3 weeks (topotecan) and 12.3 weeks (CAV) (P =.552), M edian survival was 25.0 weeks for topotecan and 24.7 weeks for CAV (P =.795 ). The proportion of patients who experienced symptom improvement was great er 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 less than or equal to.043). Grade 4 ne utropenia occurred in 37.8% of topotecan courses versus 51.4% of CAV course s (P <.001). Grade 4 thrombocytopenia and grade 3/4 anemia occurred more fr equently with topotecan, occurring in 9.8% and 17.7% of topotecan courses v ersus 1.4% and 7.2% of CAV courses, respectively(P <.001 for both). Nonhema tologic 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 sy mptoms. (C) 1999 by American Society of Clinical Oncology.