Characteristics and risk factors of cisplatin-induced ototoxicity in testicular cancer patients detected by distortion product otoacoustic emission.
OBJECTIVE
The characteristics and risk factors of the long-term ototoxic effect of cisplatin in testicular cancer patients was studied by measuring distortion product otoacoustic emissions (DPOAEs), which is a highly sensitive, new method for detecting high-frequency hearing loss.


METHODS
223 patients with a median follow-up time of 4.27 years (range 0.5-20 years) and a median age of 37 years (range 18-55 years) were assessed by DPOAE. 100 mg/m2 cisplatin were administered per cycle, in EP, BEP, VeIP, VIP or VPB regimens. The control group consisted of 40 testicular cancer patients without chemotherapy (median age 35 years, range 16-54 years). A detailed medical history evaluated audiological risk factors and hearing complaints. DPOAE was measured in eight frequencies from 750 to 8,000 Hz. Paired t test and Mann-Whitney test were used for statistical evaluation.


RESULTS
Symptomatic ototoxicity was observed in 20% of the patients. In patients receiving <or=300 mg/m2 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/m2, our method could detect significant hearing impairment at lower frequencies that are important for speech perception. At 400 mg/m2, significant amplitude change was detected at 3,000 Hz (p = 0.01); at 500-600 mg/m2, significant amplitude change was detected at 1,500, 2,000 and 3,000 Hz (p = 0.004, 0.0001 and 0.0002, respectively), and at 700 mg/m2 significant amplitude change was detected at 3,000 Hz (p = 0.01). We detected the lowest amplitudes in those 44 patients who had symptomatic ototoxicity. The only statistically significant risk factor was the cumulative dose of cisplatin; neither smoking nor noise exposure were independent risk factors.


CONCLUSIONS
DPOAE is a fast, noninvasive and reliable method in detecting late ototoxicity in testicular cancer patients. Contrary to the literature, not only high frequencies are affected. In patients receiving at least 400 mg/m2, using DPOAE we were able to detect significant hearing impairment at lower frequencies that are important for speech perception.
Biro
K
K
National Institute of Oncology, Budapest, Hungary. drbk@mail.datanet.hu
Noszek
L
L
Prekopp
P
P
Nagyiványi
K
K
Géczi
L
L
Gaudi
I
I
Bodrogi
I
I
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D006309:Hearing / Q000187:drug effects*; D034381:Hearing Loss / Q000139:chemically induced; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects*; D011159:Population Surveillance; D018570:Risk Assessment; D012307:Risk Factors; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000503:physiopathology*; D014012:Tinnitus / Q000139:chemically induced
D000970:Antineoplastic Agents; D002945:Cisplatin