The safety of combination chemotherapy with ifosfamide, cisplatin, and etoposide (ICE): Single-institution retrospective review of 108 cases

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.