SEARCH METHODS: We searched the electronic databases Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1), MEDLINE (PubMed) (1945 to 17 March 2014) and EMBASE (Ovid) (1980 to 17 March 2014). In addition, we handsearched reference lists of relevant articles and the conference proceedings of the International Society for Paediatric Oncology (2006 to 2013), the American Society of Pediatric Hematology/Oncology (2007 to 2013) and the International Conference on Long-Term Complications of Treatment of Children and Adolescents for Cancer (2010 to 2013). We scanned the International Standard Randomized Controlled Trial Number (ISRCTN) Register and the National Institute of Health Register for ongoing trials (www.controlled-trials.com) (searched on 17 March 2014).
[Show abstract][Hide abstract] ABSTRACT: Cisplatin (cis-diammine-dichloroplatinum; CDDP) is an anticancer drug that induces significant hearing loss and balance dysfunction as side effects. Cilostazol (CS, 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl) butoxy]-3, 4-dihydro-2-(1H)-quinolinone) has neuroprotective and antioxidant effects, whereas Ginkgo biloba extract (GbE) has preventive effects on CDDP-induced hearing loss in rats, and GbE enhances the antiatherogenic effect of CS by inhibiting the generation of reactive oxygen species (ROS). The purpose of this study was to investigate the effects of renexin (RXN), which contains GbE and CS, against CDDP-induced cochleo-vestibular dysfunction in rats and to elucidate the mechanism underlying the protective effects of RXN on auditory cells. Rats intraperitoneally injected with CDDP exhibited an increase in hearing threshold and vestibular dysfunction, which agreed with hair cell damage in the Organ of Corti and otoliths. However, these impairments were significantly prevented in a dose-dependent manner by pre- and co-treatment with RXN, and these preventive effects in RXN-treated rats were more prominent than those in GbE-treated rats. In a CDDP pharmacokinetic study, platinum concentration was very similar between CDDP-only treated and RXN+CDDP cotreated rats. RXN markedly attenuated CDDP-induced intracellular ROS and significantly reduced CDDP-activated expression of p-extracellular regulated kinase (ERK), BAX, cytochrome c, cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase, but increased BCL-XL expression. These results show that RXN may have a synergistic effect by strongly protecting hearing and vestibular dysfunction induced by CDDP by inhibiting ROS production, mitochondrial pathways and the ERK pathway, without interfering with CDDP pharmacokinetics. Therefore, RXN could potentially be used to reduce CDDP-related hearing loss and dizziness.
[Show abstract][Hide abstract] ABSTRACT: Childhood cancer survival rates are now nearly 80% in more developed European countries because of improved therapies and better supportive care. Platinum chemotherapy drugs, such as cisplatin and carboplatin, are the cornerstone of many effective therapeutic protocols for childhood cancer. However, the antitumor efficacy of cisplatin and carboplatin comes at the cost of ototoxicity, which affects at least 60% of pediatric patients. Although ototoxicity is not life threatening, it can have debilitating effects on patients' quality of life. Recently, many initiatives have been launched with the ultimate goal of reducing cisplatin and high-dose carboplatin ototoxicity without compromising antitumor efficacy. This review addresses the incidence of platinum ototoxicity and its clinical presentation, time course, and early diagnostic evaluation. Genetic and non-genetic risk factors for platinum-associated ototoxicity, and their predictive value, are discussed. Recent developments in the prevention of platinum ototoxicity are also summarized.
[Show abstract][Hide abstract] ABSTRACT: Background
The purpose of this study was to evaluate amifostine for protection from cisplatin-induced serious hearing loss in patients with average-risk medulloblastoma by extending a previous analysis to a much larger sample size. In addition, this study aimed to assess amifostine with serious hearing loss in patients with high-risk medulloblastoma treated with cisplatin.Methods
Newly diagnosed medulloblastoma patients (n = 379; ages 3-21 years), enrolled on one of 2 sequential St. Jude clinical protocols that included 4 courses of 75 mg/m(2) cisplatin, were compared for hearing loss by whether or not they received 600 mg/m(2) of amifostine immediately before and 3 hours into each cisplatin infusion. Amifostine administration was not randomized. The last audiological evaluation between 5.5 and 24.5 months following protocol treatment initiation was graded using the Chang Ototoxicity Scale. A grade of ≥2b (loss requiring a hearing aid or deafness) was considered a serious event.ResultsAmong average-risk patients (n = 263), amifostine was associated with protection from serious hearing loss (adjusted OR, 0.30; 95% CI, 0.14-0.64). For high-risk patients (n = 116), however, there was not sufficient evidence to conclude that amifostine prevented serious hearing loss (OR, 0.89; 95% CI, 0.31-2.54).Conclusions
Although patients in this study were not randomly assigned to amifostine treatment, we found evidence in favor of amifostine administration for protection against cisplatin-induced serious hearing loss in average-risk but not in high-risk, medulloblastoma patients.
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