TOPOTECAN, A NEW ACTIVE-DRUG IN THE 2ND-LINE TREATMENT OF SMALL-CELL LUNG-CANCER - A PHASE-II STUDY IN PATIENTS WITH REFRACTORY AND SENSITIVE DISEASE

Purpose: To assess activity and toxicity of topotecon in previously tr eated small-cell lung cancer (SCLC) patients. Patients and Methods: Pa tients with measurable SCLC, progressive after one first-line regimen, were eligible for the study. Two groups of patients were selected: (1 ) patients who failed first-line treatment less than or equal to 3 mon ths from chemotherapy discontinuation (refractory group); and (2) pati ents who responded to first-line treatment and progressed greater than 3 months after chemotherapy discontinuation (sensitive group). Topote can was administered as a 30-minute daily infusion at a dose of 1.5 mg /m(2) for 5 consecutive days, every 3 weeks. Results: One hundred one patients were entered onto the study and 403 courses were administered . Ninety-two patients (47 refractory and 45 sensitive) were eligible a nd assessable for response. Among refractory patients, there were two partial responses (PRs) and one complete response (CR), for an overall response rate of 6.4% (95% confidence interval [CI], 1.3% to 17.6%), whereas in the sensitive group, there were 11 PRs and six CRs, for an overall response rate of 37.8% (95% CI, 23.8% to 53.5%). Overall media n duration of response was 7.6 months. Median survival was 5.4 months; median survival of refractory patients was 4.7 months, whereas that o f sensitive patients was 6.9 months (P=.002). Median survival of respo nding patients was 12.5 months. Toxicity was mainly hematologic. Leuko penia, although short-lived, was universal, with grade III and IV neut ropenia occurring in 28% and 46.8% of cycles, respectively. Nonhematol ogical toxicity was mild. Fatigue/malaise was reported in 39.3% of cyc les and transient elevation of liver enzymes in 17%. Conclusion: Topot ecan has significant activity in SCLC, particularly in patients sensit ive to prior chemotherapy, with predictable and manageable toxicity. T he incorporation of topotecan in combination chemotherapy regimens for future treatment of SCLC is warranted. (C) 1997 by American Society o f Clinical Oncology.