Cancer Res Treat.  2011 Dec;43(4):260-263.

Fatal Ifosfamide-Induced Metabolic Encephalopathy in Patients with Recurrent Epithelial Ovarian Cancer: Report of Two Cases

• Shin YJ
• Kim JY
• Moon JW
• You RM
• Park JY
• Nam JH

Abstract

Central nervous system (CNS) toxicity has been reported in approximately 10-30% of patients receiving intravenous infusions of ifosfamide. Encephalopathy is a rare but serious CNS adverse reaction in these patients, and although usually transient and reversible, may cause persistent neurological dysfunction or death. Clinical features range from fatigue and confusion to coma and death. Although methylene blue can be used to treat ifosfamide-induced neurotoxicity, including encephalopathy, its mechanism of action remains poorly defined. We describe here two patients with recurrent epithelial ovarian cancer who experienced fatal encephalopathy following ifosfamide/mesna treatment.

Keyword

Encephalopathy; Ovarian epithelial cancer; Ifosfamide; Mesna; Methylene blue

MeSH Terms

Brain Diseases, Metabolic
Central Nervous System
Coma
Fatigue
Humans
Ifosfamide
Infusions, Intravenous
Mesna
Methylene Blue
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Ifosfamide
Mesna
Methylene Blue
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms

Figure

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  Fig. 1 Electroencephalogram (EEG) recording in case 1, showing frequent diffuse 1 Hz periodic triphasic waves and rhythmic delta slowing (EEG recording parameters: amplitude, 1 cm=70 µV; interval between two thick vertical lines=1 sec).

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  Fig. 2 Proposed pathogenesis pathways involved in ifosfamide neurotoxicity and the proposed sites of action of methylene blue: (1) Inhibition of extrahepatic mono-amine oxidation of chloroethylamine to chloroacetaldehyde; (2) Restoration of hepatic nicotinamide adenine dinucleomide hydrogen (NADH) oxidative functions; (3) Substitute for electron transport flavoprotein (ETF) enzyme (electron acceptor) (ada-pted from Donegan S. J Oncol Pharm Pract. 2001; 6:153-65 [13], with permission).

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