Aggravation of vincristine-induced neurotoxicity by itraconazole in the treatment of adult ALL.
In four of 14 patients with acute lymphoblastic leukemia (ALL) who received induction chemotherapy containing weekly injections of vincristine and simultaneous antifungal prophylaxis with itraconazole, unusually severe and early vincristine-induced neurotoxicity was observed. In these patients (three female, one male) paresthesia and muscle weakness of the upper/lower extremities and paralytic ileus occurred after the first or second vincristine injection. In one patient a laryngeal nerve paresis required mechanical ventilation. The neurotoxic complications were more serious than those seen in a previous series of 460 ALL patients under the identical cytostatic regimen but without itraconazole prophylaxis. The underlying mechanism is unclear. Interaction with the cytochrome P-450 system, reversal of multidrug resistance, and influence of estrogens are to be considered.
Medizinische Klinik III, J.W. Goethe-Universität, Frankfurt, Germany.
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Böhme
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Ganser
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D
Hoelzer
D000293:Adolescent; D000328:Adult; D000935:Antifungal Agents / Q000009:adverse effects*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D017964:Itraconazole / Q000009:adverse effects*; D008297:Male; D018908:Muscle Weakness / Q000139:chemically induced; D010292:Paresthesia / Q000139:chemically induced*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000188:drug therapy; D014750:Vincristine / Q000009:adverse effects*
D000935:Antifungal Agents; D000972:Antineoplastic Agents, Phytogenic; D017964:Itraconazole; D014750:Vincristine