Relationship between cisplatin administration and the development of ototoxicity.

PURPOSE: To determine the auditory toxicity associated with dose- and schedule- intensive cisplatin/gemcitabine chemotherapy in non-small-cell lung carcinoma patients. PATIENTS AND METHODS: Patients were treated with gemcitabine followed by cisplatin according to an interpatient dose-escalation scheme. Patients were randomly assigned to receive treatment once a week for 6 weeks or once every 2 weeks for 4 weeks. The following cohorts of patients were treated with a reversed schedule once every 2 weeks, in which cisplatin was followed by gemcitabine. The dose-intensity of cisplatin was equal in both schedules. Audiometric evaluations were obtained for each ear at several frequencies. Mean hearing loss after cisplatin treatment was computed for each dose level at each tested frequency in each ear at baseline and subsequent follow-up audiometry. Pure tone averages (PTAs) were also calculated. The pharmacokinetics of cisplatin was determined to study the correlation among the maximum drug concentration, the area under the curve of unbound platinum, and the development of ototoxicity. RESULTS: A total of 328 audiograms were analyzed. At the higher frequencies, a more severe hearing impairment was recorded. Most patients showed a decrease in hearing thresholds at dosages above 60 mg/m2 cisplatin at the higher frequencies. PTAs at 1, 2, and 4 kHz show a mean hearing loss of 19 dB after cisplatin administration at dosages above 90 mg/m2. Threshold shifts at 8 and 12.5 kHz after cisplatin administration were experienced at dosages above 60 mg/m2. CONCLUSION: Hearing loss after cisplatin therapy occurs mainly at high frequencies and at cisplatin dosages more than 60 mg/m2. It is more pronounced when cisplatin is given once every 2 weeks.

Reparative granuloma seen in cases of gold piston implantation after stapes surgery for otosclerosis.

OBJECTIVE: to determine the occurrence of the unusual side effect of a reparative granuloma after the implantation of a pure gold piston in cases of otosclerosis. STUDY DESIGN: a retrospective case review study of 475 stapes operations with a pure gold piston. SETTING: Department of Otorhinolaryngology of the University of Amsterdam, The Netherlands and the HNO clinic in Luenen (Brambauer) in Germany. PATIENTS: four hundred and seventy five patients (328 women, 147 men, average age: 45.2 years), who clinically and per-operatively had otosclerosis, underwent a stapedotomy using a pure gold piston prosthesis. Therapeutic intervention: in cases of suspicion of a reparative granulomas or those cases that did not have improvement of the hearing after the stapedotomy, a re-operation by transcanal approach was performed. RESULTS: in seven cases a reparative granuloma was diagnosed by this revision surgery. The postoperative incidence of these granulomas following stapedotomy using the pure gold piston turned out to be 1.5%. CONCLUSION: reparative granulomas can occur after stapedotomy with a pure gold stapes piston although the incidence is low. The role of grafting material to seal the oval window niche and the treatment of these reparative granulomas following stapes surgery are discussed.