Pazopanib: an orally administered multi-targeted tyrosine kinase inhibitor for locally advanced or metastatic renal cell carcinoma

Can J Urol. 2011 Dec;18(6):5991-7.

Abstract

Introduction: Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, responsible for approximately 90% of all kidney cancers. Prior to 2005, treatment options for patients with locally advanced and metastatic disease were limited. After the approval of sorafenib by the US Food and Drug Administration (FDA), other tyrosine kinase inhibitors (TKI) have been successively used for treating patients with advanced RCC. Pazopanib is the newest, orally bioavailable, and multi-targeted TKI, and is considered a first-line treatment option for certain patients. This review summarizes updated clinical studies, mechanism of action, and pharmacokinetics of pazopanib.

Materials and methods: Published English language literatures and data information on pazopanib for treating advanced RCC available as of March 2011 were identified and summarized.

Results: In phase II and III randomized clinical trials, pazopanib treatment resulted in considerably longer progression-free survival in patients with advanced RCC compared to placebo, with an acceptable side-effect profile. In addition, there are a few ongoing pazopanib studies including comparison to other TKIs, use for patients who have failed prior cytokine therapy, and combination with other therapeutic agents.

Conclusions: Pazopanib has been used in the United States, Europe and Canada for treating patients with advanced RCC. Currently, it is being used in good or intermediate risk RCC and shows survival benefit with acceptable adverse effects. Pazopanib is a new treatment option and needs further evaluation, particularly on its effect relative to other TKIs as well as its use in combination with other agents.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / enzymology
  • Carcinoma, Renal Cell / secondary
  • Dose-Response Relationship, Drug
  • Humans
  • Indazoles
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / enzymology
  • Kidney Neoplasms / pathology
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Pyrimidines / administration & dosage*
  • Pyrimidines / therapeutic use
  • Sulfonamides / administration & dosage*
  • Sulfonamides / therapeutic use
  • Treatment Outcome

Substances

  • Indazoles
  • Pyrimidines
  • Sulfonamides
  • pazopanib
  • Protein-Tyrosine Kinases