Ifosfamide-induced neurotoxicity

Abstract

Ifosfamide is an active chemotherapeutic agent in a wide range of gynecologic tumors; favorable response rates have been reported in ovarian (epithelial and germ cell), uterine, and cervical neoplasms. Central neurotoxicity is a known, but poorly described side effect. We report 23 patients who received a total of 75 cycles of ifosfamide, either as a single agent or in combination with other chemotherapeutic agents. Six of twenty-three (26%) experienced grade 4 neurotoxicity; clinical presentation included confusion, aphasia, hallucinations, and coma. All patients exhibited the first evidence of neurotoxicity by the end of the 24-hr infusion. Three of six patients with grade 4 neurotoxicity expired within 14 days of receiving ifosfamide. The neurotoxicity resolved over 2 to 4 days in the remaining patients. Serum albumin was normal (> 3.5 g/dl) in 63 cycles of ifosfamide not associated with neurotoxicity. When serum albumin was <3.5 g/dl, 6 of 12 cycles were associated with severe neurotoxicity ( P < 0.001). Low serum albumin (< 3.5 g/dl) appears to be associated with a high risk of severe neurotoxicity in patients receiving single-dose ifosfamide therapy.