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Pazopanib (Votrient)

Pazopanib, brand name Votrient,  is an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor (PDGFR), and KIT.  GIST cancers are usually dependent on KIT signaling, but some depend on PDGF signaling.  VEGF and PDGF are growth factors critical to the development and growth of blood vessels-- a process known as angiogenesis.  Angiogenesis plays a critical role in the growth and spread of many tumor types, with VEGF and PDGF overexpression linked to multiple cancers. 

NCI Drug Dictionary Definition:
Pazopanib hydrochloride  
The hydrochloride salt of a small molecule inhibitor of multiple protein tyrosine kinases with potential antineoplastic activity. Pazopanib selectively inhibits vascular endothelial growth factor receptors (VEGFR)-1, -2 and -3, c-kit and platelet derived growth factor receptor (PDGF-R), which may result in inhibition of angiogenesis in tumors in which these receptors are upregulated.

Manufacturer: GlaxoSmithKline (GSK).  For Pazopanib (Votrient) information at the website of GlaxoSmithKline Pharmaceuticals click here

FDA Approval for 2 other cancer types: In October 2009 the FDA approved pazopanib (Votrient) for treatment of renal cell carcinoma, as described in this FDA announcement.  Because this drug is now approved for a different cancer, it could be prescribed off-label for GIST at the discretion of a physician.  You can also read the complete prescribing information.  In APril 2012 the FDA appoved pazopanib for non-GIST soft tissue sarcoma as detailed in this announcement.

 

Clinical Trials Relevant to GIST Patients

Efficacy of Pazopanib in Gastrointestinal Stromal Tumors (GIST)
NCT Number: NCT01323400 
 
Pazopanib in Imatinib Refractory or Intolerant Gastrointestinal Stromal Tumors (GIST) 
NCT Number: NCT01391611 
 
Pazopanib in Advanced Gastrointestinal Stromal Tumors Refractory to Imatinib and Sunitinib 
NCT Number: NCT01524848

Pazopanib is being evaluated as a monotherapy, in combination with targeted therapies, and in combination with cytotoxic chemotherapy. 

Phase I Study of Pazopanib and Vorinostat  NCT01339871

Temsirolimus and Pazopanib in Patients With Advanced Solid Tumors NCT01072890

Study of Pazopanib and Ixabepilone in Patients With Solid Tumors  NCT01012362

A Randomized Double Blind Phase III Trial of Pazopanib Versus Placebo in Patients With Soft Tissue Sarcoma Whose Disease Has Progressed During or Following Prior Therapy (PALETTE) NCT00753688

Phase I, Combining Oral Topotecan With Oral Pazopanib Condition:  Advanced Solid Tumours  NCT00732420

Available Information About Results with Pazopanib

In a press release following the 33rd Congress of the European Society for Medical Oncology (ESMO) in Stockholm, Sweden, GSK stated:

“In a Phase II study of 142 patients with relapsed or refractory soft tissue sarcomas (leiomyosarcomas, adipocytic STS, synovial sarcomas and other STS types), pazopanib demonstrated activity in all tumour types except adipocytic STS.  Nearly half (46%) of patients with synovial sarcomas reached the primary endpoint of progression free survival (PFS) at 12 weeks. PFS at 12 weeks was also reached by 38% of patients with leiomyosarcomas, and 36% of patients with other STS types.”

At the 2009 ASCO meeting a presentation about a trial using pazopanib against kidney cancer showed promising results with few side effects.  You can link to the abstract below.

A randomized, double-blind phase III study of pazopanib in treatment-naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC).  Authors:   C. N. Sternberg, C. Szczylik, E. Lee, P. V. Salman, J. Mardiak, I. D. Davis, L. Pandite, M. Chen, L. McCann, R. Hawkins   Citation: J Clin Oncol 27:15s, 2009 (suppl; abstract 5021).



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