CISPLATIN OTOTOXICITY - AN ELECTROPHYSIOLOGICAL DOSE-EFFECT STUDY IN ALBINO GUINEA-PIGS

Recently, the effect of the ACTH((4-9)) analog, ORG2766, on cisplatin ototoxicity was studied by Hamers et al. (1994). This study showed tha t the ACTH((4-9)) analog partially prevents the ototoxicity of cisplat in. The authors suggested that the daily dose of 2.0 mg/kg/day for 8 d ays might have been too high to obtain full protection. Knowledge abou t dose-effect relations for cisplatin ototoxicity is rather meager. Th erefore, we conducted a basic dose-effect study for cisplatin without any concomitant additives. A follow-up of the Hamers et al. (1994) stu dy, based on dose-effect data from this paper, is presented in a compa nion paper. The effects of cisplatin on the compound action potential (CAP), cochlear microphonics (CM) and summating potential (SP) were de termined in acute experiments, in different groups of albino guinea pi gs, each group injected with a different dose of cisplatin. Daily dose s ranged from 0.7 to 2.0 mg/kg/day cisplatin (i.p.) for 8 consecutive days. Electrocochleography was performed at day 10. The measurements w ere performed over a broad range of frequencies (0.5-16 kHz). The resu lts showed clustering of the data in two groups, the first group conce rning the treatments of 1.5 and 2.0 mg/kg/day with large frequency-dep endent losses in the three cochlear potentials, the second group conce rning the treatments with lower doses of cisplatin (0.7, 1.0 and 1.25 mg/kg/day) where almost no losses in the three cochlear potentials wer e found. The threshold curves regarding the lower doses (0.7-1.25 mg/k g/day) were almost indistinguishable from the control threshold curve except at the higher frequencies (12 and 16 kHz). Thus, a marked trans ition from almost no ototoxic effect to a large effect seems to occur between cisplatin doses of 1.25 and 1.5 mg/kg/day for 8 days. The smal l difference between the effects found for 1.5 mg/kg/day and 2 mg/kg/d ay suggests that a smaller dose than the one of 2 mg/kg/day for 8 days used previously (Hamers et al., 1994) might better suit research into protection against cisplatin ototoxicity. (C) 1998 Elsevier Science B .V. All rights reserved.