Ototoxicity of high-dose cisplatin by bolus administration in patients with advanced cancers and normal hearing

Our institution undertook a phase I trial to define the toxicity of high-dose (150 to 225 mg) bolus administration (every 3 to 4 weeks) of cisplatin in patients with advanced cancers. All patients reported had baseline normal hearing. Hearing levels were measured prior to each course of chemotherapy. Audiological monitoring included conventional assessment of pure tone sensitivity at 500 to 8,000 Hz and assessment of ultra high frequencies (9,000 to 20,000 Hz). After one to two doses, 100% of patients failed to respond at 9,000 Hz and above. In the 2,000 to 8,000 Hz range, repeated administration of the drug effected successively lower frequencies with progressive loss, until a maximum threshold shift or plateau was reached at each frequency between 3,000 and 8,000 Hz. The plateau for cisplatin ototoxicity appears to fall within the moderate hearing loss range (40 to 60 dB HL) in the high frequencies. All patients complained of tinnitus and difficulty understanding speech in the presence of background noise. The pattern of pure tone audiometric alteration is consistent in all patients, all dosages, and each method of administration. The ultra high frequency alteration is prompt and dramatic.