Drug intelligence / Profile preview

pazopanib + iodine I 131

Development stage
Discontinued
Lead developer
GSK
Modality
Antibody-Radionuclide Conjugates → Antibody Conjugates → Antibody-Based Therapeutics, Beta-minus Emitters → Radiopharmaceuticals, Gamma Emitters → Radiopharmaceuticals, Small Molecules
Administration
Oral, Intramuscular
01

Overview

This combination therapy consists of the multi-targeted tyrosine kinase inhibitor (TKI) pazopanib and the radiopharmaceutical iodine I 131. It was investigated in a Phase I dose-escalation study led by the University of Washington for the treatment of patients with radioiodine-refractory well-differentiated thyroid carcinoma. Pazopanib targets vascular endothelial growth factor receptors (VEGFR-1, -2, and -3), platelet-derived growth factor receptors (PDGFR-alpha and -beta), and the stem cell factor receptor (c-KIT). The rationale for the combination was to determine if pazopanib could enhance the uptake or retention of radioactive iodine in resistant tumors. However, the trial was terminated due to significant toxicities, including dose-limiting cardiac arrhythmias and hematologic adverse events, without clear evidence that pazopanib improved iodine kinetics.

Other names
pazopanib hydrochloride + iodine I 131pazopanib + 131Ipazopanib + radioactive iodine
02

Targets

BRAF (B-Raf proto-oncogene, serine/threonine kinase)CSF1R (Macrophage colony-stimulating factor receptor)FGFR1 (Fibroblast growth factor receptor 1)PDGFRA (Platelet-derived growth factor receptor alpha)PDGFRB (Platelet-derived growth factor receptor beta)VEGFR-1 (Vascular endothelial growth factor receptor 1)VEGFR2 (Vascular endothelial growth factor receptor 2)VEGFR4 (Vascular endothelial growth factor Receptor-3)KIT (c-KIT proto-oncogene receptor tyrosine kinase)DNANIS (Human sodium iodide symporter)

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