Pharmacotherapy options in advanced renal cell carcinoma: what role for pazopanib?

Assistant Professor of Medicine, Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, DUMC 102002, Durham, NC 27710.
Clinical Medicine Insights: Oncology 01/2011; 5:349-64. DOI: 10.4137/CMO.S6087
Source: PubMed

ABSTRACT Over the last 6 years, the treatment of metastatic renal cell carcinoma (mRCC) has undergone dramatic changes. A better understanding of the pathogenesis and tumor biology of sporadic renal cell carcinoma has led to the approval of 6 drug regimens: 3 oral multi-targeted tyrosine-kinase inhibitors (sorafenib, sunitinib, and pazopanib), 2 inhibitors of the mammalian target of rapamycin (temsirolimus and everolimus), and 1 monoclonal antibody against the vascular endothelial growth factor (bevacizumab). Pazopanib, a multi-targeted tyrosine kinase inhibitor that targets VEGFR-1, -2, and-3; PDGFR-α and PDGFR-β, and c-Kit, was approved for the treatment of mRCC in October 2009, several years after the other drugs in its class. The efficacy and safety of pazopanib in Phase I, II, and III trials will be examined and its role in mRCC treatment will be described. Future studies that may clarify pazopanib's role in mRCC will be discussed. Based on pazopanib's demonstrated efficacy in treatment-naïve and cytokine-refractory patients, along with a seemingly favorable toxicity profile compared with other multi-targeted tyrosine-kinase inhibitors, pazopanib may have a unique niche in the armamentarium of treatment options for mRCC. Results from ongoing studies are awaited to confirm pazopanib's favorable efficacy-toxicity ratio, especially in comparison with the previous first-line standard-of-care, sunitinib.

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    ABSTRACT: The role of angiogenesis in the physiopathology of renal cell carcinoma is fundamental. Strategies targeting angiogenesis have been developed including VEGF and VEGFR inhibitors for the treatment of metastatic renal cell carcinoma (mRCC), in first and second line. Pazopanib is an angiogenesis inhibitor targeting VEGF receptor, PDGF receptor and c-KIT receptor. This treatment is a treatment option recommended for patients with mRCC, would be in first line or after cytokines failure. Pazopanib has been recently approved for patients with metastatic soft tissue sarcoma, after failure of at least one line of chemotherapy.
    Bulletin du cancer. 06/2014; 101(6):641-646.
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    ABSTRACT: In the past 5 years, the treatment of patients with metastatic renal cell carcinoma has changed dramatically from being largely cytokine-based with the emergence of targeted therapy. Following the elucidation of various molecular pathways in renal cell carcinoma, targeted agents (particularly vascular endothelial growth factor-targeting antiangiogenic agents) now form the backbone of most therapeutic strategies for patients with metastatic renal cell carcinoma and the outcome of treatment has improved. However, many tumors eventually develop resistance to targeted therapy due to secondary mutation of the target protein or compensatory changes within the target pathway that bypass the site of inhibition. On the other hand, there are new forms of immunotherapy that hold the promise of improving the outcome for patients with metastatic renal cell carcinoma. In this article, we describe some of these new therapies, including the anti-vascular endothelial growth factor monoclonal antibody bevacizumab, several receptor tyrosine kinase inhibitors (sorafenib, sunitinib, pazopanib, axitinib, and tivozanib), the mammalian target of rapamycin inhibitors temsirolimus and everolimus, and new immunotherapy modalities, such as anti-cytotoxic T-lymphocyte-associated antigen 4 antibody and anti-programmed cell death 1/programmed cell death-ligand 1 antibody. We also discuss their role in the current management of patients with metastatic renal cell carcinoma.
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