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Pazopanib, a VEGF receptor tyrosine kinase inhibitor for cancer therapy

Barry Sloan1, Noah S Scheinfeld

  • 1150 West 55th Street, New York, NY 10019, USA.

Current Opinion in Investigational Drugs (London, England : 2000)
|November 28, 2008
PubMed

Insights

Pazopanib, a multi-targeted tyrosine kinase inhibitor, shows antitumor activity in various cancers like renal cell carcinoma. Clinical trials indicate it is well-tolerated and effective in reducing tumor size.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Pazopanib is an oral, second-generation multi-targeted tyrosine kinase inhibitor.
  • It targets key proteins like VEGFR, platelet-derived growth factor receptor, and c-kit involved in tumor growth.

Purpose of the Study:

  • To evaluate the efficacy and safety of pazopanib in preclinical and clinical settings.
  • To assess pazopanib's antitumor activity in various cancer types, including renal cell carcinoma (RCC), breast, and lung cancer.

Main Methods:

  • In vitro potency assessment against human VEGFRs and related tyrosine receptor kinases.
  • In vivo studies using human tumor xenografts.
  • Phase I, II, and III clinical trials evaluating pazopanib as monotherapy and in combination therapies.

Main Results:

  • Pazopanib demonstrated good potency in vitro and antitumor activity in xenografts.
  • Phase I/II trials showed pazopanib was generally well-tolerated with manageable side effects (hypertension, fatigue, GI disorders).
  • Pazopanib monotherapy led to tumor size reduction and stable disease in patients with RCC, NSCLC, and gynecological tumors. Combination with lapatinib showed efficacy in breast cancer.

Conclusions:

  • Pazopanib exhibits significant antitumor activity and is a viable treatment option for various solid tumors, including RCC.
  • Ongoing trials are further investigating pazopanib's role in monotherapy and combination treatments for advanced cancers.

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