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Temozolomide + irinotecan is a combination chemotherapy regimen used primarily in the treatment of certain solid tumors, including recurrent or metastatic Ewing sarcoma, neuroblastoma, and malignant gliomas. Temozolomide is an oral alkylating agent that methylates DNA at the O6 and N7 positions of guanine, leading to DNA damage and tumor cell death[8]. Irinotecan is a topoisomerase I inhibitor that prevents religation of single-strand breaks in DNA during replication, resulting in double-stranded breaks and apoptosis[6]. The combination exhibits schedule-dependent synergy; temozolomide-induced DNA methylation enhances recruitment of topoisomerase I molecules, thereby potentiating the cytotoxic effect of irinotecan[1]. This regimen has demonstrated activity in pediatric and adult patients with refractory or relapsed solid tumors such as neuroblastoma, Ewing sarcoma, and high-grade glioma[1][3][5].
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