498 Evaluation of effect of the active metabolite of amifostine (AMI), WR-1065, on the cytotoxicity of anticancer drugs against human ovarian cancer

Abstract

Ami protects normal but not tumor tissue from cytotoxic effects of radiation and chemotherapy. The effect of amifostine's active metabolite, the free thiol, WR-1065, on the cytotoxicity of standard anticancer drugs was tested against human A2780 ovarian cancer in vitro using the sulforhodamine B assay for viability. Dose response and IC 50 values were determined in triplicate for each drug in the presence and absence of the highest nontoxic dose of WR-1065. IC 50 values (molar cone) for the drug alone and following pretreatment with WR-I065 were: taxol 1.7 vs 1.3 × 10 −8 ; cisplatin 9.2 vs 3.1 × 10 −4 ; carboplatin 9.6 vs 8.9 × 10 −3 ; doxorubicin 5.6 vs 0.08 × 10 −4 ; mitoxantrone 7,9 vs 0.18 × 10 −6 ; 5FU 8.5 vs 8.5 × 10 −5 ; vinblastine 4.5 vs 3.3 × 10 −8 , respectively. The IC 50 differences ± pretreatment with WR-1065 were not statistically significantly different. These data expand upon previous reports showing that Ami or WR-1065 does not protect tumors from the cytotoxic effects of anticancer agents. Ami's ability to protect dose-limiting toxicity to normal tissues without protection of tumor should enhance the efficacy ratio of a variety of standard anticancer drugs.