DOSE-INTENSIVE COMBINATION PLATINUM AND CYCLOPHOSPHAMIDE IN THE TREATMENT OF PATIENTS WITH ADVANCED UNTREATED EPITHELIAL OVARIAN-CANCER

BACKGROUND, The authors combined cisplatin and carboplatin together wi th cyclophosphamide to maximize platinum dose intensity in patients wi th advanced epithelial ovarian cancer (AOC). METHODS, The authors trea ted 26 consecutive, newly diagnosed patients with International Federa tion of Gynecology and Obstetrics (FIGO) Stage III/IV AOC with carbopl atin, 600 mg/m(2), on Day 1; cyclophosphamide, 250 mg/m(2), on Day 1; and cisplatin, 100 mg/m(2), on Day 8 every 4 weeks with or without pre treatment with amifostine (range, 740-1140 mg/m(2)). Platinum dose int ensity was estimated using a 4:1 conversion for equipotent doses of ci splatin and carboplatin for expression as cisplatin dose equivalents ( CDE). RESULTS. The mean administered CDE was 49.4 mg/m(2)/week, which was 79% of the planned dose. Hematologic toxicity was severe, with FIG O Grade 3-4 anemia in 81% of patients, Grade 3-4 neutropenia in 92% of patients, and Grade 4 thrombocytopenia in 90% of patients. Eleven pat ients (42%) were admitted to the hospital for febrile neutropenia and there was 1 toxic death. Sensory neuropathy greater than or equal to G rade 2 occurred in 10 patients (38%), ototoxicity greater than or equa l to Grade 2 occurred in 18 patients (69%), and 6 patients (23%) requi red long term hearing aids. Elevations in serum creatinine greater tha n or equal to Grade 2 occurred in 7 patients (27%) and greater than or equal to Grade 2 hypomagnesemia was noted in 23 patients (88%). Other Grade 3 toxicities were nausea (42%), emesis (38%), fatigue (15%), mu cositis (4%), and respiratory toxicities (4%). Twenty-two of 26 patien ts (85%) had a clinical response (19 with a complete response [CRI and 3 with a partial response). Pathologic CR was demonstrated in 10 of 2 6 patients (38%) and residual microscopic disease in 4 of 26 patients (15%) for a total pathologic response rate of 53%. The median progress ion free survival was 13.5 months and the median overall survival was 37.2 months at a median potential follow-up of 79.3 months. Three of 2 6 patients remained free of disease at 60, 71, and 103 months, respect ively. CONCLUSIONS, Although dose intensive combination platinum treat ment combined with cyclophosphamide in patients with AOC is active, it also is associated with substantial toxicity. Cancer 1998;83:1980-8. (C) 1998 American Cancer Society.