DEALING WITH INITIAL CHEMOTHERAPY DOSES - A NEW BASIS FOR TREATMENT OPTIMIZATION IN LIMITED SMALL-CELL LUNG-CANCER

Treatment of patients with small-cell lung cancer (SCLC) remains disap pointing despite high initial complete response rates. The dramatic in itial chemosensitivity of tumor cells is frustrated by the early emerg ence of chemoresistant clonogenic cells, regardless of front line trea tments. Although the dose relationship is fairly well established rega rding the response rate, its effect on survival is inconclusive. From 1980 to 1988, 202 patients with limited SCLC were included in four con secutive protocols using an alternating schedule of thoracic radiother apy and chemotherapy. Despite an increase of chemotherapy and/or total radiation doses, no significant difference was observed between the f our protocols in terms of response rate, disease free and overall surv ival. However, a retrospective analysis performed on a total of 131 co nsecutive patients led us to propose the hypothesis that a moderate in crease in the initial dose, ie first course, of cisplatin and cyclopho sphamide could improve overall survival. From 1988 to 1991, 105 patien ts were subsequently included in a large randomized trial raising this question. The treatment difference only concerned the initial doses o f cisplatin (80 vs 100 mg/m(2)) and cyclophosphamide (900 vs 1200 mg/m (2)). The trial was closed after inclusion of 105 patients, 32 months after the start of the study because al that time overall survival was significantly better in the higher-dose group (p = 0.001). The emerge nce of this debatable concept opens new directions in the therapeutic strategy of SCLC and the contribution of hematopoietic hematopoietic g rowth factors may be of great interest in the management of this disea se.