Pazopanib: an oral multitargeted tyrosine kinase inhibitor for use in renal cell carcinoma

Kourtney D LaPlant, Paige D Louzon
Annals of Pharmacotherapy 2010, 44 (6): 1054-60

OBJECTIVE: To summarize the currently available clinical data on pazopanib, as well as review the merits and adverse effects of pazopanib in the treatment of renal cell carcinoma (RCC).

DATA SOURCES: A literature search was performed of MEDLINE, PubMed, and the American Society of Clinical Oncology abstracts from January 1995 to February 2010, using the primary search terms pazopanib, GW786034, Votrient, and tyrosine kinase inhibitors.

STUDY SELECTION AND DATA EXTRACTION: All available English-language articles and trials that described the pharmacokinetics, pharmacology, pharmacodynamics, clinical activity, or adverse effects of pazopanib were reviewed.

DATA SYNTHESIS: Pazopanib is a second-generation multitargeted tyrosine kinase inhibitor (TKI) that has exhibited antiangiogenic and antitumor activity. Phase 1 clinical trials have established the safety and tolerability of pazopanib 800 mg orally daily. Phase 2 and 3 studies have shown promising activity in RCC, including treatment naïve or cytokine-pretreated patients, demonstrating a greater rate of total disease control with pazopanib compared to placebo. Activity has also been shown in a variety of other cancers, including ovarian cancer, non-small-cell lung cancer, breast cancer, and soft tissue sarcoma. The most common adverse effects of pazopanib include nausea, diarrhea, hypertension, hair depigmentation, and elevated transaminase levels. Adverse effects are most commonly Grades 1-2. Other Phase 3 trials are ongoing in RCC, including a comparison to sunitinib, another TKI used in RCC, as well as trials in other tumor types.

CONCLUSIONS: Current data suggest pazopanib to be a viable treatment option as first-line therapy for advanced RCC. Data are awaited comparing pazopanib to other TKIs. Until results of head-to-head trials conducted of the various agents are available, it cannot be said whether pazopanib is more tolerable or efficacious than currently available therapies.

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