Analysis of risk factors for cisplatin-induced ototoxicity in patients with testicular cancer

Abstract

Summary This study evaluates the degree and relevance of persisting ototoxicity after cisplatin-based standard-dose chemotherapy for testicular cancer, with emphasis on identification of potential factors for an increased risk of this late sequel. Hearing thresholds of 86 patients with a median age of 31 years (range 21-53 years) and a median follow-up time of 58 months (range 15-159 months) were assessed by conventional pure-tone audiometry. Interviews were conducted evaluating the patients' history with special regard to audiological risk factors, as well as circumstances of ototoxic symptoms. Details concerning treatment and patient variables were extracted retrospectively from the patients' charts. An additional screening programme assessed current body functions, blood parameters and other late toxicities. Symptomatic ototoxicity persisted in 20% of patients (59% tinnitus, 18% hearing loss, 23% both), while 10% had experienced completely reversible ototoxic symptoms for a duration of 1-18 months after treatment. Symptoms were bilateral in 81 % of patients. Hearing thresholds were compatible with cisplatin-induced hearing loss in 42% of audiograms performed. Subjective (history) and objective (audiogram) findings were not always consistent. The following statistically significant risk factors for ototoxicity were established: high cumulative dose of cisplatin (P < 0.0001); history of noise exposure (P = 0.006). Additionally, high doses of vincristine (P = 0.001) seemed to result in reversible ototoxic symptoms. No other independent risk factors were identified. In conclusion, persisting ototoxicity represents a clinical sequel for approximately 20% of testicular cancer patients treated at standard dose but may affect more than 50% of patients receiving cumulative doses of cisplatin > 400 mg m-2. Previous noise exposure may also result in a threefold increased risk for cisplatin ototoxicity. Future studies should use these risk factors as important stratification criteria for trials aiming at the evaluation and prevention of cisplatin-induced ototoxicity.Keywords: chemotherapy; ototoxicity; long-term toxicity; testicular cancerThe ototoxic potential of the chemotherapeutic agent cisplatin was recognized 2 decades ago (Piel et al, 1974). Despite the widespread use of cisplatin in standard treatment protocols for testicular, ovarian, head and neck, lung and other types of cancers, data on the frequencies of ototoxicity are not consistent, and risk factors have not been clearly identified so far. The measurement of the auditory function is limited because of the different diagnostic methods used for objective assessment and the subjective perception of symptoms; patients' characteristics, such as age or noise exposure, may additionally influence the hearing ability and different definitions of 'normal' and 'abnormal' hearing thresholds may also cause further discrepancies in reported results.In the current study the auditory function was evaluated in a homogeneous group of young men receiving cisplatin-based com...

High prevalence of cisplatin-induced ototoxicity in Cape Town, South Africa

“…[6,9,10] In a recent study investigating a cohort of Japanese head and neck cancer patients, the threshold cumulative dosage of cisplatin was 200 mg/m 2 , above which average hearing thresholds were significantly reduced in these patients. [11] Our data indicate that SA patients who received higher cumulative cisplatin dosages during chemotherapy were more likely to develop significant hearing loss, with median cumulative dosages of 180.70 mg/m 2 and 236.84 mg/m 2 for the ototoxicity-free and ototoxicity groups, respectively.…”

“…[8][9][10] The majority of studies investigating cisplatininduced ototoxicity have been performed on European and South American patient cohorts, [4][5][6]10] with only a single study examining the development of ototoxicity in Japanese head and neck cancer patients. The incidence rate of cisplatin-induced ototoxicity was reported as 77.3% in the 44 Japanese patients investigated.…”

Proposed comprehensive ototoxicity monitoring program for VA healthcare (COMP-VA)

“…Previous studies that examined extent of preexposure hearing as a potential risk factor for ototoxicity have conflicting results [24][25]. Differences across studies can be understood in terms of the differences in testing methodology, specifically the different test frequency ranges used.…”

Hearing loss in the developing world: Evaluating the iPhone mobile device as a screening tool

“…Noise exposure may result in a three-fold increased risk of hearing loss with cisplatin. [17,18] Ototoxicity monitoring is aimed at preventing or minimising the progression of hearing loss through prospective hearing assessments. It is the most reliable method of detecting ototoxicity prior to development of symptomatic hearing loss [19] and permits clinicians to counsel patients, possibly modify treatment regimens, and rehabilitate hearing.…”

“…[16] Cisplatin, a commonly used antineoplastic drug, is known to cause irreversible dose-dependent ototoxicity [6,17] leading to HFSNHL. Noise exposure may result in a three-fold increased risk of hearing loss with cisplatin.…”