ICE（イホマイド・シスプラチン・エトポシド）療法の安全性：単一施設の108連続症例の検討から

The Safety of Combination Chemotherapy with Ifosfamide,Cisplatin,and Etoposide (ICE): Single-institution Retrospective Review of 108 Cases

Ⅰ．はじめに

　固形腫瘍に対する化学療法は，膠芽腫に対するテモゾロミド単剤投与²⁹⁾を除き，一般的には多剤併用療法が用いられている．この中でアルキル化剤（イホマイド）・白金製剤（シスプラチン）・トポイソメラーゼⅡ阻害剤（エトポシド）を併用したICE療法は，1986年にGöbelら¹³⁾が精巣外原発の胚細胞腫瘍への有効性を示して以来，頭蓋外胚細胞腫，非小細胞性肺癌，小細胞性肺癌，非ホジキン性悪性リンパ腫，卵巣癌，再発ユーイング肉腫^{1,9-12,15,19)}などで広く有効性が示されてきた．

　一方で頭蓋内腫瘍に対しては，MAKEI 89 Studyにて精巣外胚細胞腫瘍に対するICE療法の有効性が報告されたが，その一部に頭蓋内胚細胞系腫瘍が含まれ¹⁴⁾，その後，髄芽腫^25,31)，原始神経外胚葉性腫瘍³¹⁾，嗅神経芽腫¹⁸⁾，脳幹部膠芽腫^5,26)などで有効性が報告されてきた．

　本報告では当科における1997年以降のICE療法施行症例を後方視的に検討し，有害事象について明らかにすることを目的とした．この中で，2005年5月から骨髄抑制，腎機能障害，聴力障害を参考にした減量基準に従った投与量の調整を行ったが，減量による治療効果，有害事象への影響にも着目した．

　Purpose: The adverse effects of combination chemotherapy of ifosfamide, cisplatin, and etoposide (ICE) were evaluated in the treatment of various intracranial brain tumors. Methods: 108 cases were retrospectively reviewed. The histological diagnosis was newly diagnosed or recurrent germ cell tumor in 45 cases, medulloblastoma in 19, primitive neuroectodermal tumor (PNET) in 7, anaplastic ependymoma in 6, recurrent glioblastoma in 13, and others in 18 cases. Patients received 1-8 cycles of ICE chemotherapy with or without radiation therapy. The adverse effects were analyzed based on the the clinical or laboratory examinations. Results: Common Terminology Criteria for Adverse Events ver. 3.0 (CTCAE v3.0) grade 4 neutropenia, anemia, and thrombocytopenia occurred in 81.4%, 14.8%, and 35.2% of patients, respectively. Non-hematological adverse effects, including infection, elevated aspartate aminotransferase (AST)/alanine aminotransferase (ALT), high or low levels of serum sodium, and seizure, occurred in 26.8%, 29.6%, 28.7%, and 11.1% of patients, respectively. One patient died of opportunistic infection with neutropenia. The proportion of ICE cycles associated with CTCAE v3.0 grade 4 neutropenia, transfusion of platelets, and elevated AST/ALT significantly decreased after enforcement of dose reduction criteria. Conclusion: The high rate of adverse effects requires close follow up and dose reduction.