| Abstract: |
Sunitinib and axitinib are two oral, small-molecule agents that emerged from the same drug discovery program. They were rationally designed for selective inhibition of receptor tyrosine kinases (RTK), critically involved in human tumor malignancies. Sunitinib, the more extensively studied of the two, has demonstrated unprecedented antitumor activity in two phase II studies of cytokine-refractory metastatic renal cell carcinoma (mRCC) and statistically significant superiority over interferon-alfa as first-line therapy in patients with mRCC. These data have established sunitinib as a new reference standard of care in the first-line mRCC setting. Axitinib has also demonstrated significant antitumor activity in the cytokine-refractory mRCC setting, as well as shown encouraging results as second-line therapy in mRCC patients, refractory to prior RTK inhibition. In this chapter, we will discuss each compound in turn, briefly reviewing the preclinical and phase I development of each, before summarizing the clinical data available to date for the use of each in mRCC, including biomarker data for both drugs and discussion of data for sunitinib in different patient populations, in combination with other targeted agents, and at different dosing schedules. © 2009 Humana Press. |
