COMBINATION OF IRINOTECAN AND ETOPOSIDE FOR TREATMENT OF REFRACTORY OR RELAPSED SMALL-CELL LUNG-CANCER

Purpose: To determine the response rate, survival and toxicity of irin otecan (CPT-11), a topoisomerase I inhibitor, combined with etoposide, a topoisomerase II inhibitor, in refractory or relapsed small-cell lu ng cancer (SCLC). Patients and Methods: Twenty-five patients with refr actory or relapsed SCLC were entered onto the trial. All 25 patients h ad been pretreated with some form of cisplatin-based combination chemo therapy and had also received previous etoposide- or anthracycline-con taining chemotherapy. The median time off chemotherapy was 6.7 months (range, 0.9 to 23.5). Patients were treated at 4-week intervals using CPT-11 (9 starting dose of 70 mg/m(2) intravenously on days 1, 8, and 15) plus etoposide (80 mg/m(2) intravenously on days 1 to 3), with a s ubsequent dose based on toxicity In addition, recombinant human granul ocyte colony-stimulating factor (rhG-CSF; 2 mu g/kg/d) was given from day 4 to day 21, except on the days of CPT-I 1 administration. Results : All patients were assessable for toxicity and survival. Twenty-four patients were assessable for response. There were 14 partial responses (PRs) and three complete responses (CRs), for an overall response rat e of 71% (95% confidence interval, 53% to 89%). The median response du ration was 4.6 months. Median survival was 271 days. Major toxicities were myelosuppression (predominantly leukopenia) and diarrhea. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 56% and 20% of pati ents, respectively. Grade 3 to 4 diarrhea was observed in 4%. There wa s one treatment-related death due to severe myelosuppression. Conclusi on: A combination of CPT-11 and etopaside with rhG-CSF support is an a ctive therapy against refractory or relapsed SCLC and deserves to be s tudied more extensively in a phase III trial. (C) 1998 by American Soc iety of Clinical Oncology.