THE IMPORTANCE OF PLATINUM DOSE INTENSITY IN TREATMENT OF EPITHELIAL OVARIAN-CANCER

In a retrospective analysis of 294 patients with FIGO stages In and TV epithelial ovarian cancer treated with different polychemotherapy regimens in two prospective randomised phase III trials between 1981 and 1988, we evaluated the importance of platinum dose intensity for survival. The median survival time of 55 patients who were treated without platinum was 11 months, whereas 205 patients who were treated with a polychemotherapeutic regimen with a platinum dose intensity of 8 mg/m(2)/week showed a median survival time of 26 months. Of 34 patients who were treated with a platinum dose intensity of 18 mg/m(2)/week, more than 50% are still alive and therefore the median survival time has not yet been reached (Mantel test p<0.001). These findings support the hypothesis that an increase in platinum dose intensity during the first treatment regimen leads to an increase in survival of patients with advanced epithelial ovarian cancer. Since 1991 we have been investigating in a prospectively randomized clinical trial whether a combination of carboplatinum and cisplatinum with a planned dose intensity of 43.75 mg/m(2)/week is feasible and able to improve survival in comparison with standard polychemotherapy (cyclophosphamide/cisplatinum) with a planned dose intensity of 25 mg/m(2)/week. Evaluation of toxicity of 268 cycles of carboplatinum/cisplatinum in 58 patients showed that a platinum dose intensity of 33.4 mg/m(2)/week was achievable with acceptable toxicity. Results with regard to therapeutic efficacy of this high dose therapy are expected within the next year.