Ototoxicity From Cisplatin Therapy in Childhood Cancer

Abstract

Cisplatin has been associated with hearing damage. It is usually irreversible, bilateral, and characterized by high-frequency sensorineural hearing loss. This study was carried out to identify impairment of hearing function in children and adolescents with cancer after cisplatin therapy. Twenty-three survivors of childhood cancer treated with cisplatin at our Unit from 1991 to 2004 performed tympanometry, pure tone audiometry, transient otoacoustic emissions, and distortion product otoacoustic emissions (DPOAE). The median age at diagnosis was 12.3 years and the median total dose of cisplatin received was 406 mg/m2. Fifty-two percent of patients had bilateral and in the high frequencies range hearing loss on audiometry. Transient otoacoustic emission and DPOAE abnormalities were detected in 22% and in 71% of the patients, respectively. We found a high concordance between the findings of audiometry and DPOAE (P=0.01). There was no influence of sex and number of ototoxic drugs other than cisplatin on hearing loss. There was a trend for younger age and higher cumulative dose of cisplatin to be associated with greater severity of hearing damage. Our data provide further evidence on hearing damage due to cisplatin therapy in children. The high incidence of patients with hearing function abnormalities found in this study and in previous reports highlights the importance of monitoring hearing function in children and adolescents undergoing cisplatin therapy, or as early as possible at follow-up. This study also demonstrates that DPOAE should be used for screening of hearing abnormalities and, once hearing damage is identified, patients require expert audiologic pediatric evaluation and (where indicated) use of hearing aids and/or speech therapy.

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

“…With an incidence of 55.1%, this report of cisplatininduced hearing loss illustrates that SA adult patients may be at higher risk than their European and South American counterparts, for whom incidence rates of 23 -50% have been reported. [4][5][6] We suspect that this trend would be similar for many other hospitals around SA. Since not all patients receive audiological monitoring during high-dose cisplatin treatment and this study was only conducted at a single major Western Cape hospital, our findings may under-represent the incidence of cisplatin-induced ototoxicity.…”

“…[4][5][6] However, some studies have reported elevated hearing thresholds in up to 100% of cisplatin-treated cancer patients. [1] Limited data are available on the incidence of drug-induced hearing impairment in Africa.…”

“…[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.…”

Assessing the risk of transplant-related complications and individually tailoring the HSCT procedure in children and adolescents—is it possible?

“…Younger age and higher cumulative dose of cisplatin seem to be associated with greater severity of hearing damage. 69 We recommend that patients who receive ototoxic treatment should undergo expert audiologic paediatric evaluation before HSCT.…”

Cisplatin up‐regulates ICAM‐1 expression in endothelial cell via a NF‐κB dependent pathway

“…Cisplatin or cis-diamminedichloroplatinum II is one of the most effective chemotherapeutic agents used in the treatment of a wide variety of both pediatric and adult malignancies, (1,2) and it is believed to kill cells through interaction with DNA, mainly by formation of various DNA adducts, which lead to initiation of apoptosis. (3,4) Apart from being useful, it shows toxicity to the human body and leads to severe side-effects such as dose-dependent cumulative nephrotoxicity, (5)(6)(7) ototoxicity, (8)(9)(10) neurotoxicity, (11)(12)(13)(14) and an increased incidence of thrombosi, (15) following cisplatinbased combination chemotherapy, including combinatorial therapies with antiangiogenic agents. (16) The presence of these dangerous side-effects has prompted research to achieve a better understanding of the biochemical mechanisms underlying the toxicities.…”