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cyclophosphamide + methotrexate + vandetanib

Development stage: Unknown
Lead developer: AstraZeneca
Modality: Small Molecules
Administration: Oral

Overview

A combination therapy consisting of metronomic cyclophosphamide (50 mg daily), methotrexate (2.5 mg days 1-2 weekly), and vandetanib (100-300 mg daily, with 200 mg being the maximum tolerated dose). This regimen combines traditional chemotherapeutic agents administered in a metronomic schedule with a multi-targeted tyrosine kinase inhibitor that has antiangiogenic properties. The combination has been studied in metastatic breast cancer patients with modest clinical activity observed in heavily pretreated populations.

Targets

SHMT2 (Serine hydroxymethyltransferase 2)MRP3 (Multidrug resistance-associated protein 3)DHFR (Dihydrofolate reductase)DNAVEGFR3 (Vascular endothelial growth factor receptor 3)VEGFR-1 (Vascular endothelial growth factor receptor 1)VEGFR2 (Vascular endothelial growth factor receptor 2)RET (Rearranged during transfection receptor tyrosine kinase)EGFR T790M (Epidermal growth factor receptor T790M mutant)

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