Combination versus alternating chemotherapy in small-cell lung cancer

The major obstacles in the treatment of small-cell lung cancer (SCLC) are tumor recurrence and the emergence of drug resistance to chemotherapeutic agents. Using alternating non-cross-resistant combination regimens is an attractive strategy, but the efficacy and toxicities are still controversial.

Previously untreated SCLC patients were randomly assigned to standard CEOV therapy (cyclophosphamide, epirubicin, vincristine = oncovin, and etoposide = VP-16) or CEOV alternating with CAM therapy (cyclophosphamide, ACNU and methotrexate). Chemotherapy was repeated every 4 weeks for a total of eight cycles. Complete and partial responders were administered thoracic irradiation.

Between July 1987 and July 1993, 150 patients were enrolled and 123 were evaluable. There was no significant superiority in the treatment outcome for CEOV-CAM therapy over CEOV therapy in terms of overall response rate (51% vs 71%), complete response rate (9% vs 35%), median survival time (9.5 months vs 12.0 months) and 2-year survival rate (7% vs 13%). Both patients with limited disease and extensive disease had equal response rates to the CEOV regimen (70% and 71%, respectively). However, patients with limited disease had a significantly higher response rate to the CEOV-CAM regimen than did patients with extensive disease (65% vs 36%, p = 0.04). Toxicities for both treatment arms were comparable. Patients who achieved complete or partial response received thoracic irradiation and had significantly longer survival than responders who did not receive thoracic irradiation (14.0 months vs 12.0 months, p = 0.02). There were equal chances of tumor recurrence in the chest and at distant sites (66% vs 67%) in the CEOV arm. However, in the CEOV-CAM arm, tumors were more likely to occur in the chest than in distant sites (86% vs 36%) (p = 0.0016).

We concluded that alternating chemotherapy provides no therapeutic advantage compared with four-regimen combination chemotherapy in terms of tumor response, median survival and 2-year survival rate for SCLC patients. Early thoracic irradiation should be applied to achieve better local control and less distant recurrence for chemotherapy responders.