pISSN 1598-2998, eISSN 2005-9256 http://dx.doi.org/10.4143/crt.2011.43.4.260 Open Access Central nervous system (CNS) toxicity has been reported in approximately 10-30% of patients re- ceiving 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, in- cluding 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. Key words Encephalopathy, Ovarian epithelial cancer, Ifosfamide, Mesna, Methylene blue Fatal Ifosfamide-Induced Metabolic Encephalopathy in Patients with Recurrent Epithelial Ovarian Cancer: Report of Two Cases toethane sulfonate (mesna), a synthetic thiol compound that binds to toxic species of ifosfamide in the bladder to form stable nontoxic thioether com- pounds. Ifosfamide and mesna can both have adverse effects in the central nervous system (CNS), with 10-30% of ifosfamide-treated patients ex- periencing CNS toxicity [2-6]. These neurotoxicities are dose dependent and may be fatal. Furthermore, the mechanism of action and factors pre- disposing to ifosfamide-induced encephalopathy are poorly understood. Methylene blue (MB) can be used to treat these encephalopathies, but its mechanism of action is unclear. In this report, we describe two patients with recurrent epithelial ovarian cancer who experienced fatal ifosfamide- Cancer Res Treat. 2011;43(4):260-263 Case Report You-Jung Shin, MD Ji-Young Kim, MD Jei-Won Moon, MD Rae-Mi You, MD Jeong-Yeol Park, MD, PhD Joo-Hyun Nam, MD, PhD Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea + + + + + + + + + + + + + + + + + + + + + C+or+res+po+nd+en+ce:+Je+on+g-Yeol P+ark,+M+D,+Ph+D+ + + + + + D+ep+ar+tm+ent+of+O+bs+tetr+ics+an+d+Gy+ne+co+log+y,+ + + + A+san + Me+dical + + + Center, + + + University+of + + + + Ulsan + + Colle+ge + + + + + + + + + + + + + + + + + + + + + + + o+f M+e+dic+ine+, P+un+gn+ap+2-+do+ng+,S+on+gp+a-g+u,+ + + + S+eo+ul+13+8-7+36+, K+or+ea+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + T+el:+82+-2+-30+10+-3+64+6 + + + + + + + + + + + + F+ax+: 8+2-2+-4+77+-73+31+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + E+-m+ai+l: c+atg+ut+1-0@+ha+nm+ai+l.n+et + + + + + + + + + R+ec+eiv+ed+Ju+ly+7,+20+10+ + + + + + + + + + + + A+cc+ep+ted+ S+ep+tem+be+r 2+9,+20+10+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + I n t r o d u c t i o n Ifosfamide is an alkylating agent frequently used to treat ovarian, tes- ticular, cervical, and head and neck cancers, as well as lymphomas and soft tissue sarcomas. Frequent side effects of ifosfamide include myelo- toxicity, hemorrhagic cystitis and neurotoxicity (mental confusion, drowsi- ness, hallucinations, disorientation, and coma) [1]. Although the use of ifosfamide was initially limited by severe hemorrhagic cystitis, this prob- lem was resolved by the concurrent administration of sodium 2-mercap- 260 Copyright ⓒ 2011 by the Korean Cancer Association This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/3.0/)whichpermitsunrestrictednon-commercialuse,distribution, andreproductioninanymedium,providedtheoriginalworkisproperlycited. │http://www.cancerresearchandtreatment.org│ │http://www.e-crt.org│