Assessment of the Protective Effects of Amifostine against Cisplatin-Induced Toxicity

Abstract

OBJECTIVE: The goals of this study were to determine whether the toxicity of cisplatin, a chemotherapeutic alkylating agent, could be reduced by the use of amifostine and to determine whether amifostine alone could cause ototoxicity. STUDY DESIGN: Prospective, animal study. METHODS: Auditory brainstem response click threshold, latencies, and blood work were used to measure ototoxicity, nephrotoxicity, and myelotoxicity before and 4 weeks after treatment. Groups of guinea pigs received either cisplatin alone (30 mg/kg), amifostine (1000 mg/kg), cisplatin plus amifostine (1000 mg/kg), or no agent. RESULTS: Amifostine reduced the hearing loss caused by cisplatin for many animals. Amifostine partially protected against cisplatin-induced ototoxicity and renal toxicity. We did not find evidence for myelotoxicity owing to cisplatin in this sample. CONCLUSION: Amifostine may have a role in reducing toxicity or permitting larger doses of cisplatin to be given, but toxicity can still be significant even with protection.