We've recently reported ethacrynic acid inhibits the efflux of anthracycline ant ibiotics in isolated systems & intact cells & enhances the toxicity of anthracyc lines towards cancer cells. Ethacrynic acid is known to enhance alkylating agent efficacy. Because ethacrynic acid should enhance efficacy of both anthracycline & alkylating agents, we propose a phase I trial to determine:feasibility of comb ining ethacrynic acid, mitoxantrone, thiotepa & cisplatin &, to determine maxima lly tolerated dose of thiotepa using GM-CSF to ameliorate hematopoetic toxicity.
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