Drug intelligence / Profile preview

pazopanib + gemcitabine + docetaxel (Memorial Sloan Kettering Cancer Center)

Development stage
Phase 2
Lead developer
GSK
Modality
Small Molecules
Administration
Oral, Intravenous
01

Overview

The combination of pazopanib, gemcitabine, and docetaxel was an investigational neoadjuvant regimen evaluated by Memorial Sloan Kettering Cancer Center (MSKCC) for the treatment of high-grade, localized extremity soft tissue sarcoma. Pazopanib is an oral multitargeted tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors (VEGFR-1, -2, and -3), platelet-derived growth factor receptors (PDGFR-α and -β), and c-Kit, primarily acting as an antiangiogenic agent. Gemcitabine is a nucleoside analog that inhibits DNA synthesis by replacing cytidine during DNA replication and inhibiting ribonucleotide reductase. Docetaxel is a taxane that promotes microtubule assembly and inhibits disassembly, leading to cell cycle arrest. A Phase Ib/II trial (NCT01507480) was initiated to assess the safety and efficacy of this triplet therapy prior to surgical resection; however, the study was terminated early due to slow patient accrual and significant toxicities, including hepatotoxicity.

Other names
gemcitabine, docetaxel, and pazopanib
02

Targets

CSF1R (Macrophage colony-stimulating factor receptor)DNA polymerase familyFGFR1 (Fibroblast growth factor receptor 1)FGFR3 (Fibroblast growth factor receptor 3)VEGFR-1 (Vascular endothelial growth factor receptor 1)VEGFR4 (Vascular endothelial growth factor Receptor-3)VEGFR2 (Vascular endothelial growth factor receptor 2)KIT (c-KIT proto-oncogene receptor tyrosine kinase)PDGFRA (Platelet-derived growth factor receptor alpha)PDGFRB (Platelet-derived growth factor receptor beta)RNR (Ribonucleotide reductase)TUBB (Tubulin (alpha and beta subunits))DNA

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