Methylene blue in the treatment and prevention of ifosfamide-induced encephalopathy: report of 12 cases and a review of the literature

Ifosfamide is an alkylating agent used in the treatment of a variety of sol id tumours. Ten to 15% of patients treated with ifosfamide develop an encep halopathy. Methylene blue (MB) may be used in the treatment of this encepha lopathy. The purpose of this study was to evaluate the neuroprotective effe ct of MB in these patients and to review the literature. Between 1993 and 1 997, 52 patients (age 16-77 years) with solid tumours were treated with ifo sfamide in dosages ranging from 3 to 5 g m(-2) q3w when given in combinatio n schedules and up to 12 m(-2) q4w when given as a single agent. Twelve pat ients developed central nervous system (CNS) depression, defined as Nationa l Cancer Institute Common Toxicity Criteria (NCI-CTC) neurocortical toxicit y grade 2 or higher. Eight were treated with MB at a dose of 6 x 50 mg day( -1) intravenously (i.v.). Four recovered fully within 24 h, two recovered p artially after 24 h and completely after 48 h while two recovered only afte r 72 h. Four patients did not receive MB and all recovered only after 48 h. Three patients received prophylaxis with MB at a dose of 4 x 50 mg day(-1) i.v. for the subsequent chemotherapy cycles. Two developed milder encephal opathy; one had no CNS depression at all. We conclude that MB is an effecti ve treatment for ifosfamide-induced encephalopathy. Our findings suggest th at it may also be used as a prophylactic agent. (C) 2000 Cancer Research Ca mpaign.