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 initially high complete response rates. The dramatic initial chemosensitivity of tumor cells is rapidly thwarted by the ear ly emergence of chemoresistant clonogenic cells, regardless of front l ine treatments. Although a dose-response relationship is well establis hed its effect on survival is inconclusive. From 1980 to 1988, 202 pat ients with limited SCLC were included in four consecutive trials using an alternating schedule of thoracic radiotherapy and chemotherapy. De spite an increase in chemotherapy and/or the total radiation dose, no significant difference was observed between the four trials in terms o f response, disease-free or overall survival. However, a retrospective analysis performed on a total of 131 consecutive patients led us to p ostulate that a moderate increase in the initial dose, i.e. first cour se, of cisplatin and cyclophosphamide, could improve overall survival. From 1988 to 1991, 105 consecutive patients were included in a large randomized trial to address this question. The difference in treatment options only concerned the initial doses of cisplatin (80 vs. 100 mg/ m(2)) and cyclophosphamide (900 vs. 1200 mg/m(2)). According to the tr iangular test used in this study the trial was closed after inclusion of 105 patients, 32 months after the start of the study because, at th at time, overall survival was significantly better in the higher-dose group (p = 0.001). This debatable concept of dose-intensity having an impact on survival offers new possibilities for the management of SCLC . The contribution of hematopoietic support may help to validate this concept.