PR-1. ASSESSMENT OF AMIFOSTINE PROTECTIVE EFFECTS AGAINST CISPLATIN INDUCED TOXICITY

Abdulmohsen Hussain (MB, FRCSC, Kuwait), Brian Blakley (FRCSC, Canada)

Objective: The goal of this animal study was to determine whether the maximum tolerated dose (MTD) of Cisplatin, a chemotherapeutic alkylating agent could be increased by the use of Amifostine (Ethyol, formerly called WR27-21) a cytoprotective agent originally selected as a clinically usable radioprotector from more than 4,400 compounds in the 1950’s.

Study Design: Prospective, animal study

Methods: Auditory brain response (ABR) and blood work was done to evaluate ototoxicity, nephrotoxicity, and myelotoxicity before and 4 weeks after treatment.  Treatment groups of 5 guinea pigs received cisplatin (15mg/kg or 30 mg/kg), cisplatin plus amifostine (1000 mg/kg) amifostine alone or no agent.A total of 25 guinea pigs.

Results: Amifostine increased the MTD of cisplatin to 30 mg/kg for many animals.  Amifostine was a better protector for renal and myelotoxicity than for ototoxicity, however, the differences in protection may indicate that different biochemical mechanisms are responsible for toxicity.

Conclusions: Amifostine may have a role in reducing toxicity or permitting larger doses of Cisplatin to be given.

 
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