A phase II study of topotecan and cyclophosphamide with G-CSF in patients with advanced small cell lung cancer

We conducted a multicenter phase II study to evaluate the efficacy and safety of the combination of topotecan and cyclophosphamide for patients with advanced small cell lung cancer (SCLC).

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 600 mg/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.

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) (CI: 51-135 days) and the median overall survival was 9 months (5 days-37 months) (CI: 210-330 days). The two-year survival rate was 21%.

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 some 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.