[Trials of modulating the MDR1 phenotype in malignant hemopathies]

The first trials with modifier agents and chemotherapy were conducted in myeloma, with verapamil and VAD. The objective responses observed could not be undoubtfully rapported to the addition of modifier agent. The cyclosporin A could be given at 10 to 18 mg/kg/d by IV route during few days, without nephrotoxicity. A bone marrow toxicity was due to the modification of cytostatic pharmacokinetics. The remissions observed with addition of cyclosporin A or quinine in acute leukemia could be due to either the high dose of ara-C given with daunorubicin or mitoxantrone, or to the drug pharmacokinetic modifications, or the P-gp inhibition on leukemic cells (or probably a combination of these factors). Randomized trials are now going on.