AGGRAVATION OF VINCRISTINE-INDUCED NEUROTOXICITY BY ITRACONAZOLE IN THE TREATMENT OF ADULT ALL

In four of 14 patients with acute lymphoblastic leukemia (ALL) who rec eived induction chemotherapy containing weekly injections of vincristi ne and simultaneous antifungal prophylaxis with itraconazole, unusuall y severe and early vincristine-induced neurotoxicity was observed. In these patients (three female, one male) paresthesia and muscle weaknes s of the upper/lower extremities and paralytic ileus occurred after th e first or second vincristine injection. In one patient a laryngeal ne rve paresis required mechanical ventilation. The neurotoxic complicati ons were more serious than those seen in a previous series of 460 ALL patients under the identical cytostatic regimen but without itraconazo le prophylaxis. The underlying mechanism is unclear. Interaction with the cytochrome P-450 system, reversal of multidrug resistance, and inf luence of estrogens are to be considered.