PHASE 3 TRIAL COMP MEC W/ MEC + PSC833 IN PTS W/ RELAPSED &REFRACTORY AML

Pennsylvania State Univ Hershey Med Ctr, Hershey PA

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Abstract

This is a phase III randomized trial of the Eastern Cooperative Oncology Group to look at a new therapy for AML. Only 4 patients will be enrolled here. The majority of patients with AML who achieve CR will relapse and chemotherapy for patients who relapse is largely unsatisfactory. The three chemotherapy drugs to be used have previously been shown to be effective in AML, inducing a 35-87% complete remission rate depending on the patient group and dose of chemo. Amoung, the best best understood mechanisms of relapse is multidrug resistance (MDR), mediated by the multidrug transporter P-glycoprotein and encoded by the mdr1 gene. PSC 833 is a non-nephrotoxic analog of cyclosporine and is a modulator of MDR. In this study, MEC will be given with or without PSC 833. It is expected that PSC833 inhibition of the MDR will result in enhanced retention of mitoxantrone and etoposide by the leukemic cells and enhance therapeutic benefit. Because there are potential pharmakokinetic interactions between PSC 833 and MDR-related cytotoxins, the doses of mitoxantrone and etoposide will be reduced.