General Information

Votrient (pazopanib) is a vascular epidermal growth factor receptor (VEGFR) tyrosine kinase inhibitor which acts at all three isoforms: VEGFR-1, VEGFR-2 and VEGFR-3. VEGF is a chemical signal produced by cells that stimulates the growth of new blood vessels. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate. When VEGF is overexpressed, it can contribute to disease. Solid cancers need an adequete blood supply or they will not be able to grow. Hence, cancer that can express VEGF are able to grow and metastasize.

Votrient is specifically indicated for the treatment of patients with advanced renal cell carcinoma.

Votrient is supplied as a tablet designed for oral administration. The recommended initial dose is 800 mg orally once daily without food (at least 1 hour before or 2 hours after a meal). The dose of Votrient should not exceed 800 mg.

Clinical Results

FDA Approval
The FDA approval of Votrient was based on the results of a randomized, double-blind, placebo-controlled, multicenter study in 435 subjects with locally advanced and/or metastatic RCC who had received either no prior therapy or one prior cytokine-based systemic therapy. The subjects were randomized to receive Votrient 800 mg once daily or placebo once daily. The primary objective progression-free survival (PFS); the secondary endpoints included overall survival (OS), overall response rate (RR), and duration of response. The median progression free survival for the overall population was 9.2 months in the Votrient arm versus 4.2 months in the placebo group (P<0.001). The median progression free survival for the treatment-naïve subgroup was 11.1 months versus 2.8 months and in the Cytokine pre-treated subgroup 7.4 months versus 4.2 months. In the Votrient arm, there was a 30% response rate (complete response + partial response) versus 3% in the placebo arm. The median duration of response was 58.7 weeks in the Votrient arm.

Side Effects

Adverse events associated with the use of Votrient may include, but are not limited to, the following:

• Diarrhea
• Hypertension
• Hair color change
• Nausea
• Fatigue
• Anorexia
• Vomiting

Mechanism of Action

Votrient (pazopanib) is a vascular epidermal growth factor receptor (VEGFR) tyrosine kinase inhibitor which acts at all three isoforms: VEGFR-1, VEGFR-2 and VEGFR-3. VEGF is a chemical signal produced by cells that stimulates the growth of new blood vessels. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate. When VEGF is overexpressed, it can contribute to disease. Solid cancers need an adequete blood supply or they will not be able to grow. Hence, cancer that can express VEGF are able to grow and metastasize.

Literature References

Rini BI Vascular endothelial growth factor-targeted therapy in metastatic renal cell carcinoma. Cancer 2009 May 15;115(10 Suppl):2306-12

Sonpavde G, Hutson TE, Sternberg CN Pazopanib, a potent orally administered small-molecule multitargeted tyrosine kinase inhibitor for renal cell carcinoma. Expert Opinion on Investigational Drugs 2008 Feb;17(2):253-61

Hutson TE, Sonpavde G, Galsky MD Targeting growth factor and antiangiogenic pathways in clear-cell renal cell carcinoma: rationale and ongoing trials. Clinical Genitourinary Cancer 2006 Dec;5 Suppl 1:S31-9.

Additional Information

For additional information regarding Votrient or renal cell carcinoma, please visit the Votrient web page.