title: Irinotecan therapy in a 12-year-old girl with recurrent brain stem glioma and without functional polymorphisms in UGT1A1 activity: case report.
abstract: A 10-year-old girl was diagnosed with astrocytoma grade 2. Immuno-chemo-radiotherapy (interferon, ranimustine, and radiation), second-line chemotherapy (carboplatin and etoposide, 7 cycles) and third-line chemotherapy (ifosfamide, carboplatin, and etoposide) was given to treat progressive disease. Finally, irinotecan therapy was initiated and led to dramatic clinical improvement. Irinotecan is metabolized by carboxylesterase to form an active SN-38, which is further conjugated and detoxified by UDP-glucuronosyltransferase (UGT) to yield its beta-glucuronide. The polymorphic UGT isoenzyme, UGT1A1 has genetic variants which decrease in SN-38 glucuronidating capacity and could help predict irinotecan-associated toxicity. The patient suffered excessive toxicity with low-dose irinotecan although no functional polymorphism in UGT1A1 was identified. We suggest that irinotecan offers an effective treatment option for children with recurrent brain stem glioma and other genetic variants except UGT1A1 may be a risk factor for irinotecan-induced toxicity.
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Nagoya 466-8560, Japan. kaz-ishi@med.nagoya-u.ac.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Kajita
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Noda
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshida
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D020295:Brain Stem Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives*; D002648:Child; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000503:physiopathology; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D007970:Leukopenia / Q000139:chemically induced; D008279:Magnetic Resonance Imaging; D011110:Polymorphism, Genetic
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D014453:Glucuronosyltransferase; D002166:Camptothecin