A Phase II Study of Topotecan and Cyclophosphamide with G-CSF in Patients with Small Cell Lung Cancer with Poor Prognostic Factors

Abstract

Purpose: We conducted a multicenter phase II study to evaluate the efficacy and safety of the combination of topotecan and cyclophosphamide for patients with small cell lung cancer (SCLC) with poor prognostic factors. Patients and Methods: Patients were eligible if they had newly diagnosed extensive stage SCLC or if they had SCLC that progressed more than three months after completion of the first chemotherapy regimen. Patients were treated every 21 days with cyclophosphamide 600mg/m2 IV on day 1 and topotecan 1.0 mg/m2 on days 1 to 5. Filgrastim was administered for 10 days starting on day 6. Patients were evaluated for objective tumor response, time to tumor progression, overall survival and toxicity. Results: Forty–two eligible patients were treated. Seventeen patients (40.5%) had an objective response including 4 (9.5%) complete remissions (CR). Fifteen patients (35.7 %) had stable disease. There are 2 patients known to be alive at the time of this report: one with stable disease at 26 months and another with a CR at 37 months. The median number of cycles completed was 6 (range 1-12). The major toxicities were grades 3 and 4 neutropenia (73.8%), grades 3 and 4 anemia (35.7%) and grades 3 and 4 thrombocytopenia (50%). Five patients died during the first cycle of chemotherapy. The median time to progression was 3 months (range 5 days-36 months) )[95% confidence interval (CI),2 months to 4.5 months] for all patients. The median overall survival was 9 months (range 5 days – 37 months) [95% CI, 7 months to 11 months]. The two-year survival rate was 21%. Conclusions: The combination of topotecan and cyclophosphamide is highly active in small cell lung cancer. Myelosuppression is the major toxicity and is rapidly reversible in most patients. The incidence of treatment-related mortality was comparable to other intensive chemotherapy regimens. This incidence is unacceptably high and indicates better selection criteria are needed in order to exclude patients at excessive risk of morbidity.