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 irinotecan (CPT-11), a topoisomerase I inhibitor, combined with etoposide, a topoisomerase II inhibitor, in refractory or relapsed small-cell lung cancer (SCLC). Patients and Methods: Twenty-five patients with refractory or relapsed SCLC were entered onto the trial. All 25 patients had been pretreated with some form of cisplatin-based combination chemotherapy and had also received previous etoposide- or anthracycline-containing 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 subsequent dose based on toxicity In addition, recombinant human granulocyte 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 rate of 71% (95% confidence interval, 53% to 89%). The median response duration 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 patients, respectively. Grade 3 to 4 diarrhea was observed in 4%. There was one treatment-related death due to severe myelosuppression. Conclusion: A combination of CPT-11 and etopaside with rhG-CSF support is an active therapy against refractory or relapsed SCLC and deserves to be studied more extensively in a phase III trial. (C) 1998 by American Society of Clinical Oncology.