[Detection of ototoxic effect of cisplatin with otoacoustic emission in testicular cancer patients].
The aim of the research was to detect the acute and long-term ototoxic effect of cisplatin in testicular cancer patients, using OAE (otoacoustic emission), a highly sensitive new objective method, for detecting medication-related hearing loss. Secondary objective was to evaluate the risk factors that contribute to hearing loss. In the study for acute hearing loss ten males with different histological types of testicular germ cell tumor were examined with TOAE (transiently evoked otoacoustic emission), before the 1st and after the 5th day of their 1st cycle of cytostatic therapy. Patients received 100 mg/m 2 cisplatin per cycle (20 mg/m 2 for five days). Ten age-matched healthy volunteers of good hearing and without treatment were also examined with the same method. Wilcoxon and paired t-tests were used for statistical evaluation. In this acute phase study no differences were found either in otological physiological examination, in conventional audiometry, or in tympanometry. There were no statistically significant differences in amplitude either before and after therapy, or between patient and control group. No patient complained of hearing loss or tinnitus. In the long-term hearing loss study 223 cured patients were assessed by DPOAE (distorsion product otoacoustic emission). Patients received 100 mg/m 2 cisplatin per cycle, in EP, BEP, VeIP, VIP or VPB regimens. The control group consisted of 40 testicular cancer patients without chemotherapy. A detailed medical history of the patient and his family evaluated audiological risk factors and hearing complaints. Before DPOAE, otoscopic examination and tympanometry tests were used to exclude any conductive component. DPOAE was measured in eight frequencies from 750 to 8,000 Hz. Paired t-test, Mann-Whitney test and stepwise discriminant analysis were used for statistical evaluation. Symptomatic ototoxicity was observed in 20% of the patients. In patients receiving < or =300 mg/m 2 cisplatin, no amplitude changes were detected. Beyond this dose, hearing impairment proved to be dose-dependent. Contrary to the literature, not only high frequencies were affected. In patients receiving > or =400 mg/m 2 , our method could also detect significant hearing impairment at lower frequencies that are important for speech perception (1000-3000 Hz). The lowest amplitudes were detected in those patients who had symptomatic ototoxicity. The only statistically significant risk factors were the cumulative dose of cisplatin and age; neither smoking nor previous noise exposure proved to be risk factors. As the life expectancy of testicular cancer patients matches in most cases the life expectancy of healthy males, studying long-term side effects is of great importance. OAE is a fast, noninvasive and reliable method in detecting ototoxicity in testicular cancer patients. Cisplatin dose regimens should be reduced to the minimum required for cure, based on a risk-adapted treatment.
Semmelweis Egyetem Patológiai Tudományok Doktori Iskola, Budapest. birok@oncol.hu
Krisztina
K
Biró
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016022:Case-Control Studies; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D034381:Hearing Loss / Q000139:chemically induced* / Q000503:physiopathology; D006801:Humans; D008297:Male; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects*; D012307:Risk Factors; D013736:Testicular Neoplasms / Q000188:drug therapy*; D013997:Time Factors; D055815:Young Adult
D000970:Antineoplastic Agents; D002945:Cisplatin