Dasatinib and Temozolomide Combination

The combination of dasatinib and temozolomide is a therapeutic regimen that has been investigated in clinical trials for various central nervous system (CNS) tumors, particularly in pediatric populations with relapsed or refractory disease. ## Pharmacological Profile Dasatinib is a multi-kinase inhibitor that targets several tyrosine kinases, including BCR-ABL and SRC family kinases. Temozolomide is an alkylating agent that damages DNA and triggers cell death. When combined, these drugs appear to have complementary mechanisms of action that may enhance their anti-tumor effects. In clinical trials, this combination has been studied with various dosing regimens. One phase I trial established a maximum tolerated dose (MTD) for the combination as dasatinib 65 mg/m² twice daily with temozolomide 75 mg/m² daily, administered for 21 days followed by 7 days rest in repeating 28-day cycles[1]. ## Clinical Development The combination has been investigated in several clinical settings: 1. In pediatric patients with relapsed or refractory primary CNS tumors, where preliminary evidence of clinical benefit was observed[1]. 2. As part of more complex regimens, such as the RIST protocol (Rapamycin, Irinotecan, Sprycel/dasatinib, Temozolomide) for neuroblastoma[2][3]. 3. In combination with radiation therapy for newly diagnosed malignant gliomas[7]. The most common toxicities observed with this combination were hematologic, including thrombocytopenia. Other reported adverse events included somnolence, confusion, hypokalemia, and infections[1][3]. Interestingly, research suggests that dasatinib-induced autophagy is enhanced when combined with temozolomide in glioma, which may contribute to its therapeutic effects[6]. ## Current Status The combination continues to be investigated in various clinical trials. The RIST regimen (which includes dasatinib and temozolomide along with rapamycin and irinotecan) has shown promising results in MYCN-amplified relapsed or refractory neuroblastoma, significantly improving progression-free survival and overall survival compared to irinotecan/temozolomide alone[2][3][4]. This combination represents an approach to targeting multiple pathways simultaneously in aggressive pediatric cancers, with ongoing research to optimize its efficacy and safety profile.

Brand names

SprycelTemodarTemodal

Other names

dasatinib + TMZdasatinib + temozolomide combination