Irinotecan has been increasingly used for treatment of pediatric cancers over the past decade. Irinotecan has modest single-agent activity against common childhood solid tumors, and the low incidence of myelosuppression seen with protracted administration makes it well-suited for combination chemotherapy regimens. Data from mouse xenograft models and clinical trials suggest the activity of irinotecan can be improved by the addition of temozolomide, vincristine, or bevacizumab. These observations have led to focused investigation in at least seven different types of childhood cancer. This report summarizes the progress made in understanding the spectrum of activity, pharmacokinetics, pharmacogenetics, toxicity profile, and mechanisms of resistance of this agent. Also reviewed are the different schedules and routes of administration that have been investigated in pediatric clinical trials. Finally, potential applications for future use are discussed, including novel combinations with targeted therapies.
Keywords: Irinotecan, pediatric cancer, neuroblastoma, Ewing sarcoma, rhabdomyosarcoma, Childhood Cancers, myelosuppression, chemotherapy regimens, temozolomide, vincristine, bevacizumab, chemotherapeutic agent, Camptotheca acuminata, camptothecin derivative, drug-enzyme-DNA complex, colorectal cancer, medulloblastoma, glioblstoma, xenograft models, ABCG2 transporter system, Children's Oncology Group, dactinomycin, cyclophosphamide, Neuroblastoma Therapy, I-MIBG therapy, Hepatoblastoma, Renal Tumors, topotecan, SN-38, High-grade Glioma, vascular endothelial growth factor, FDA, front-line salvage therapy, atropine, prophylactic cephalosporins, Glucuronidation, enzyme UGT1A1, cytochrome P3A4, Irinotecan + Gefitinib, ABCG2 expression, Trabectedin, Bortezomib, Temsirolimus, PARP Inhibitors, viral-directed enzyme-prodrug therapy, Pegylated SN-38
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