Itraconazole and multidrug resistance: possible effects on remission rate and disease-free survival in acute leukemia

Abstract

Itraconazole, a triazole antifungal agent, has been reported to reverse drug resistance against daunorubicin in acute leukemia. In a subanalysis from a double-blind, placebo-controlled trial examining the effects of itraconazole on the prevention of fungal infections in neutropenic patients, we studied the effects of itraconazole on remission rate and disease-free survival in patients with acute lymphoblastic (ALL) and acute myelogenous leukemia (AML) receiving remission induction treatment schedules containing daunorubicin (DNR). Eleven ALL and 17 AML patients received itraconazole and 12 ALL and 25 AML patients were given placebo. Among AML patients the remission rate was slightly higher in the itraconazole group, whereas the disease-free survival was higher among ALL patients given itraconazole. In AML patients DFS was comparable in both groups but the number of high-risk patients in the itraconazole group was higher. These preliminary results may suggest a role for itraconazole in reversing multidrug resistance. Larger trials, however, are required to substantiate these findings and to correlate them with its in vitro effects on multidrug resistance.