Ototoxicity due to cis-diamminedichloroplatinum in the treatment of ovarian cancer: influence of dosage and schedule of administration.

Ototoxicity associated with administration of cisplatin was assessed in four groups of patients suffering from advanced ovarian carcinoma. The purpose was to determine the influence of dosage, schedule of administration, and long-term treatment on pure-tone thresholds and other auditory parameters. One hundred and forty-five serial audiograms were obtained in 60 patients and compared with baseline audiograms. The treatment protocol consisted of two different dosages (low--50 mg/m2 and high--100 mg/m2) and three different schedules of administration (short--6 months, extended--12 months, and treatment in blocks--intervening months in which cisplatin was withheld). Using a conservative definition of auditory toxicity and statistical analyses of pure-tone threshold differences between groups, the results indicated that the low dose-short treatment regimens with either monthly administration of cisplatin, or administration in blocks, were the least ototoxic. Ototoxicity was found to increase with increasing cumulative dosages. Hearing loss was primarily in the high frequencies. The most severe ototoxic effects, which include tinnitus and hearing loss in the speech frequency range, were associated with the administration of high dosages over a short period of time. Individual variability in susceptibility to ototoxicity necessitates systematic audiometric monitoring throughout therapy.