Prevention of Platinum-Induced Hearing Loss in Children with Cancer

Prevention of Platinum-Induced Hearing Loss in Children with Cancer

Prevention of Platinum-Induced Hearing Loss in Children with Cancer


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Prevention of Platinum-Induced Hearing Loss in Children with Cancer
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Which medications are effective in the prevention of platinum-induced hearing loss in children with cancer?


A systematic review of four studies.


Platinum-based therapies such as cisplatin, carboplatin, oxaliplatin, or a combination of these, are commonly used in the management of malignant neoplasms in children. A significant adverse effect associated with the use of these therapies, however, is ototoxicity, or hearing loss. Although there is a wide variation in the reported frequency of platinum-induced hearing loss with the use of these therapies in children with cancer, it is estimated to be as high as 90.1%.


The purpose of this review was to assess the effectiveness of medications to prevent platinum-based therapy–induced hearing loss in children with cancer and to determine the effects of these medications on antitumor efficacy, adverse effects other than hearing loss, and quality of life in these children.

Platinum-based therapy (such as cisplatin, carboplatin, oxaliplatin, or a combination of these) added to an otoprotective medical intervention was compared with platinum-based therapy combined with placebo or no additional treatment or another otoprotective medical intervention. The same platinum analogues with the same cumulative or individual doses and infusion duration were not, but should have been, used in both treatment groups.

Outcomes of interest were hearing loss, tinnitus, overall and event-free survival, tumor response, adverse effects, and quality of life. Three randomized controlled trials (RCTs) and one controlled clinical trial (CCT) were included in the review.

Two RCTs (including children with osteosarcoma) and one CCT (including children with hepatoblastoma), for a total of 149 participants, compared amifostine with no additional treatment. A total of 72 participants received amifostine and 77 received no otoprotective intervention. The amifostine dose was 740 mg/m2 given in a 15-minute IV infusion immediately prior to the platinum dose (28 children with osteosarcoma received intraarterial doses and the rest IV).

The third RCT, a study of 109 participants with hepatoblastoma, compared sodium thiosulfate (STS) with no additional treatment: 57 participants were given STS and 52 received no additional treatment. The STS dose was 20 g/m2 given in a 15-minute IV infusion, six hours after platinum treatment.


The results of this review demonstrate low-certainty evidence for amifostine and moderate-certainty evidence for STS as otoprotective interventions.

In terms of adverse effects, more vomiting occurred with amifostine (low-certainty evidence), but there was no significant difference in renal toxicity between treatment groups and no children experienced cardiotoxicity. There was low-certainty evidence of a good or partial tumor response. The amfostine studies did not report overall survival, event-free survival, or quality of life.

In the case of STS, there was no significant difference between groups in terms of adverse effects. Low-certainty evidence was reported in tumor response, overall survival, and event-free survival. Quality of life was not reported. However, these results should be viewed with caution and “no evidence of effect,” as stated in this review, is not the same as “evidence of no effect.”

Adverse effects are common in the treatment of patients diagnosed with cancer. It should be noted that this review demonstrated a medium-level certainty in the use of STS as an otoprotective intervention and in vomiting as an adverse effect of amifostine use.

SOURCE DOCUMENTvan As JW, et al. Medical interventions for the prevention of platinum-induced hearing loss in children with cancer. Cochrane Database Syst Rev 2019;5:CD009219.

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