Role of sunitinib and sorafenib in the treatment of metastatic renal cell carcinoma

Jon J Hiles, Jill M Kolesar
American Journal of Health-system Pharmacy: AJHP 2008 January 15, 65 (2): 123-31

PURPOSE: The role of sunitinib and sorafenib in the treatment of metastatic renal cell carcinoma (mRCC) is reviewed.

SUMMARY: Sunitinib malate is a potent inhibitor of vascular endothelial growth factor (VEGF) receptors, FMS-like tyrosine kinase 3 (FLT3), c-KIT, and platelet-derived growth factor (PDGF), which give the drug its direct antitumor and antiangiogenic properties. Sunitinib is currently approved as a second-line treatment of mRCC in patients who have either not responded to or who are not eligible to receive interleukin-2. Clinical trials of sunitinib have found similar rates of partial response, disease stabilization, and progression-free survival. Sorafenib inhibits VEGF receptors, PDGF receptors, FLT3, RAF-1, and BRAF in vitro and has been shown to prevent the growth of tumors but not to reduce tumor size. Sorafenib has been proven to improve survival in a novel randomized discontinuation trial and a Phase III randomized, placebo-controlled trial. No studies have directly compared the effectiveness of sunitinib to sorafenib in the treatment of advanced renal cell carcinoma. Sunitinib and sorafenib share a similar mechanism of action and primarily target tumor angiogenesis by inhibiting a variety of tyrosine kinases; the agents have similar toxicity, with the exception of an increased risk of hypertension associated with the use of sorafenib. Sorafenib does not result in tumor shrinkage, but sunitinib significantly reduces tumor size.

CONCLUSION: The tyrosine kinase inhibitors sorafenib and sunitinib offer improved outcomes for patients with mRCC, but they are far short of a cure. Despite the introduction of sorafenib and sunitinib, palliative care is still an acceptable treatment option for mRCC because of the disease's extremely poor prognosis.

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