Medical interventions for the prevention of platinum-induced hearing loss in children with cancer

Platinum-based therapy, including cisplatin, carboplatin, oxaliplatin or a combination of these, is used to treat a variety of paediatric malignancies. One of the most important adverse effects is the occurrence of hearing loss or ototoxicity. In an effort to prevent this ototoxicity, different otoprotective medical interventions have been studied. This review is the second update of a previously published Cochrane review. To assess the efficacy of medical interventions to prevent hearing loss and to determine possible effects of these interventions on anti-tumour efficacy, toxicities other than hearing loss and quality of life in children with cancer treated with platinum-based therapy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 6), MEDLINE (PubMed) (1945 to 8 July 2016) and EMBASE (Ovid) (1980 to 8 July 2016). In addition, we handsearched reference lists of relevant articles and we assessed the conference proceedings of the International Society for Paediatric Oncology (2006 up to and including 2015), the American Society of Pediatric Hematology/Oncology (2007 up to and including 2016) and the International Conference on Long-Term Complications of Treatment of Children and Adolescents for Cancer (2010 up to and including 2015). We scanned the International Standard Randomized Controlled Trial Number (ISRCTN) Register (www.isrctn.com) and the National Institute of Health Register (www.clinicaltrials.gov) for ongoing trials (both searched on 12 July 2016). Randomized controlled trials (RCTs) or controlled clinical trials (CCTs) evaluating platinum-based therapy together with an otoprotective medical intervention versus platinum-based therapy with placebo, no additional treatment or another protective medical intervention in children with cancer. Two review authors independently performed the study selection, data extraction, risk of bias assessment and GRADE assessment of included studies, including adverse effects. We performed analyses according to the Cochrane Handbook for Systematic Reviews of Interventions. We identified two RCTs and one CCT (total number of participants 149) evaluating the use of amifostine versus no additional treatment in the original version of the review; the updates identified no additional studies. Two studies included children with osteosarcoma, and the other study included children with hepatoblastoma. Children received cisplatin only or a combination of cisplatin and carboplatin, eit