Cyclophosphamide, vincristine, cisplatin, VP-16 and radiation therapy in extensive small-cell lung cancer

Patients with extensive small-cell lung cancer were given induction chemotherapy consisting of cyclophosphamide, vincristine, cisplatin, and etoposide (COPE) every 3 weeks for four cycles. Responding patients then received chest and elective whole-brain irradiation. Patients presenting with brain metastases received therapeutic brain irradiation during the first cycle of chemotherapy. No maintenance therapy was given, but two late intensification cycles of COPE were given at weeks 24 and 48. Among the 34 evaluable patients, the response rate to induction chemotherapy was 59%, with 10% achieving a complete response (CR) and 49%, a partial response (PR). Of the 18 patients who completed chest irradiation, 3 achieved a CR, producing an overall CR rate of 18%. Five patients completed the projected course of treatment. The median duration of response for all patients was 8 months (range, 2–30+ months) and the median survival was 9 months (range, 1–30+ months). Complete responders had a median response duration of 9 months and a median survival of 11 months. This regimen produced significant myelosuppression, with 5 neutropenic deaths (13%) occuring in the 38 patients evaluable for toxicity; an additional 16% required hospitalization for fever while neutropenic. Only six patients (13%) had nadir platelet counts of 3 with no episodes of thrombocytopenic hemorrhage. Nausea, vomiting, and neurotoxicity were mild to moderate in all patients. One patient with no evidence of disease died of radiation pneumonitis at 6 months. While producing significant toxicity, this regimen did not result in a CR rate or survival advantage that would suggest its superiority over standard regimens for small-cell lung cancer.