PHASE-II STUDY OF TOPOTECAN IN PATIENTS WITH EXTENSIVE-STAGE SMALL-CELL CARCINOMA OF THE LUNG - AN EASTERN-COOPERATIVE-ONCOLOGY-GROUP TRIAL

Purpose: To determine the response rate and survival of chemotherapy-n aive patients with extensive-stage small-cell lung cancer (SCLC) treat ed with topotecon, and to determine the relationship of topotecan phar macokinetics with response and toxicity. Patients and Methods: Forty-e ight patients with previously untreated, extensive-stage SCLC received 2.0 mg/m(2) of topotecan daily for 5 days. The first 13 patients were treated without colony-stimulating factor (CSF) support; the next 35 patients received 5 mu g/kg of granulocyte-colony-stimulating factor ( G-CSF) for 10 to 14 days starting on day 6. Cycles were repeated every 3 weeks for a maximum of four cycles. patients who had a partial resp onse to topotecan after four cycles, stable disease after two cycles, or progressive disease at any time received salvage chemotherapy with cisplatin and etoposide. Topotecan pharmacokinetics were measured usin g a four-point sampling scheme. Results: Of 48 patients, none had a co mplete response and 19 had a partial response, for an objective respon se rate of 39% (95% confidence interval [CI], 25.2% to 53.0%), The med ian response duration was 4.8 months (95% CI, 3.0 to 7.3). After a med ian follow-up duration of 18.2 months, the overall median survival tim e was 10.0 months (95% CI, 8.2 to 12.7); the 1-year survival rate was 39% (95% CI, 25.2% to 53.0%). Eight of 34 patients (24%) who received salvage chemotherapy responded. Four of 17 patients who did not respon d to first-line therapy with topotecan responded to cisplatin and etop oside. The most common toxicity was hematologic. Ninety-two percent of patients treated without G-CSF developed grade 3 or 4 neutropenia, co mpared with 29% who received G-CSF. However, the incidence of neutrope nic fevers was similar between the two groups (8% and 11%, respectivel y), and one patient in each group died of neutropenic fevers. There we re no differences in objective tumor response, duration of response, t ime to treatment failure, or survival between the 13 patients who ente red the study before G-CSF administration wets mandated and the 35 pat ients who entered after and received G-CSF. There was poor correlation between the WBC count and absolute neutrophil counts (ANCs) and both the area under the curve (AUC) and maximum concentration (C-max) of to tal topotecan in plasma, There was no correlation between the tumor re sponse and either AUC or C-max of total topotecan. Conclusion: The act ivity of topotecan in extensive-stage SCLC noted this study warrants f urther investigation of this agent in phase III clinical trials. (C) 1 996 by American Society of Clinical Oncology.