First-line chemotherapy with epirubicin, paclitaxel, and carboplatin for advanced ovarian cancer:: A phase I/II study of the Arbeitsgemeinschaft Gynakologische Onkologie Ovarian Cancer Study Group

Purpose: Despite the progress that has been achieved over the years, survival rates in patients with advanced ovarian cancer are still disappointing. New methods to improve the efficiency of first-line chemotherapy are warranted. One method to improve results is to add more non-cross-resistant drugs to platinum-paclitaxel combination regimens. Anthracyclines are among the candidates for incorporation as the "third drug" into first-line regimens for advanced ovarian cancer. Patients and Methods: We performed a phase I/II trial with escalating doses of epirubicin (60, 75, and 90 mg/m(2)) combined with fixed doses of paclitaxel and carboplatin in 27 previously untreated patients with advanced gynecologic malignancies. Results: Dose-limiting toxicity occurred at dose level 2 (75 mg/m(2) epirubicin) and consisted of myelosuppression (neutropenia, thrombocytopenia). No dose-limiting, nonhematologic toxicities were observed. The maximum tolerable dose was epirubicin 60 mg/m(2) (E) combined with a 3-hour infusion of paclitaxel 175 mg/m(2) (T) and carboplatin AUC 5 (Carbo). Preliminary analysis indicated promising activity against ovarian cancer. Conclusion: The three-drug combination ET-Carbo, given according to the outlined dose and schedule, should be considered for further phase III evaluation, A randomized German-French intergroup trial comparing ET-Carbo with carboplatin-paclitaxel has already been initiated. J Clin Oncol 17:46-51, (C) 1999 by American Society of Clinical Oncology.