A RANDOMIZED STUDY OF CARBOPLATIN VS SEQUENTIAL IFOSFAMIDE CARBOPLATIN FOR PATIENTS WITH FIGO STAGE-III EPITHELIAL OVARIAN-CARCINOMA

In a study designed to compare response rates of patients with stage I II epithelial ovarian carcinoma to ifosfamide and carboplatin, 152 pat ients were randomised to receive either sequential therapy with three cycles of ifosfamide followed by three cycles of carboplatin, or to si x cycles of single agent carboplatin. Ifosfamide was given every 3 wee ks in a dose of 5 gm m-2 as a 24 h infusion with mesna, 1 gm M-2 by i. v. bolus prior to ifosfasmide, 3 gm m-2 with ifosfamide, and 1 gm m-2 as an 8 h infusion after ifosfamide. Carboplatin was given in a dose o f 400 mg m-2 by short i.v. infusion every 4 weeks. Sixty-eight evaluab le patients were randomised to sequential ifosfamide/carboplatin, and 67 to single agent carboplatin. Median follow-up is 36 months (range 5 .5 82.3). After three cycles of treatment two patients in the ifosfami de/carboplatin arm achieved complete remission (CR), and 12 partial re mission (PR) for an overall response rate of 29%, whereas in the carbo platin arm ten patients achieved CR, and 23 PR, for an overall respons e rate of 63% (P = 0.0008). Seven of 15 patients with progressive dise ase, and nine of 20 patients with stable disease at the initial respon se evaluation, following three cycles of ifosfamide, subsequently resp onded to carboplatin therapy so that the final response rate to the co mplete regimen was 65% for the ifosfamide/carboplatin arm, compared to 71% for the carboplatin arm (NS). For the ifosfamide/carboplatin arm, median recurrence free survival and overall survival were 14.1 months and 18.7 months. Corresponding figures for the carboplatin arm were 1 4.5 months and 21.5 months (NS). Both treatments were generally well t olerated. However 47% of patients in the ifosfamide/carboplatin arm de veloped alopecia sufficient to require a wig, compared to only 2% in t he carboplatin arm. Ifosfamide is clearly less effective, and more tox ic than carboplatin. Ifosfamide failures can however be effectively sa lvaged by subsequent carboplatin treatment. Ifosfamide cannot be recom mended for single agent therapy in ovarian carcinoma, however the comb ination of carboplatin plus ifosfamide might be a suitable treatment t o be tested in a future randomised study against carboplatin alone.