Pazopanib: a Review in Advanced Renal Cell Carcinoma

Abstract

Pazopanib (Votrient®), an orally administered multi-targeted tyrosine kinase inhibitor that predominantly inhibits vascular endothelial growth factor receptor-1, -2 and -3, platelet-derived growth factor receptor-α and -β, and the stem cell factor receptor c-Kit, is approved in the EU, the USA and other countries for the treatment of advanced renal cell carcinoma (RCC). In randomized controlled trials in patients with advanced, predominantly clear-cell RCC, pazopanib significantly improved progression-free survival (PFS) compared with placebo in both treatment-naïve and cytokine-pretreated patients and, as a first-line therapy, was noninferior to intermittent sunitinib with respect to PFS. However, pazopanib had a tolerability profile that was distinguishable from that of sunitinib, based on lower incidences of most adverse events, particularly those associated with discomfort, such as fatigue, hand-foot syndrome and stomatitis. Consistent with this, health-related quality of life (HR-QOL) measures evaluating fatigue, hand/foot soreness and mouth/throat soreness significantly favoured pazopanib over sunitinib. In addition, significantly more patients expressed a preference for pazopanib over sunitinib, primarily because of better overall HR-QOL and less fatigue. Efficacy and tolerability findings from these prospective clinical trials have been substantiated by evidence from a number of retrospective studies evaluating unselected real-world patients with metastatic RCC who received pazopanib (or sunitinib) as a first-line therapy. Thus, data from clinical trials supplemented with that from clinical practice support the use of pazopanib as a standard or alternative first-line treatment for advanced or metastatic RCC.

Recent advances on anti-angiogenesis receptor tyrosine kinase inhibitors in cancer therapy

“…Pazopanib is a multi-kinase inhibitor on VEGFR-1/2/3, PDGFR-α/β, and c-Kit receptor [36]. The study VEG105192 conducted by Sternberg et al compared pazopanib to placebo in 435 advanced RCC patients [37].…”

A Precision Strategy to Cure Renal Cell Carcinoma by Targeting Transglutaminase 2

“…Temsirolimus [7] and everolimus [8] were selected for mammalian target of rapamycin complex 1 (mTORC1) inhibition. Cabozantinib [9], pazopanib [10], and axitinib [11] Int. J. Mol.…”

Genetic polymorphisms associated with adverse reactions of molecular-targeted therapies in renal cell carcinoma

“…A number of novel drugs based on molecular targets relating to the progression of renal cell carcinoma (RCC) have been developed and used in clinical practice, drastically improving the prognosis of patients with metastatic RCC [1,2]. However, specific adverse reactions which are not popular in the treatment with ordinal cytotoxic cancerous drugs are being reported [3][4][5]. A crucial issue in the safe and effective targeted chemotherapy is to identify mechanisms and predictive markers of adverse drug reactions.…”