Dosing strategies and optimization of targeted therapy in advanced renal cell carcinoma

Within the past decade, treatment options for metastatic renal cell carcinoma have expanded dramatically. Currently, seven targeted agents are approved for use in metastatic renal cell carcinoma and have superseded the use of parenteral cytokine therapy with interleukin-2 or interferon, the former standards of care for metastatic renal cell carcinoma. Targeted agents include inhibitors of the vascular endothelial growth factor pathway (i.e. sorafenib, sunitinib, pazopanib, axitinib, and bevacizumab) and inhibitors of the mammalian target of rapamycin pathway (i.e. temsirolimus and everolimus). These newer therapies have been shown to improve progression-free survival compared with previous approaches. Because most of these targeted agents are taken orally, responsibility for dose administration has shifted to patients, which might result in variable adherence. Additionally, with new treatments for metastatic renal cell carcinoma comes the challenge of selecting dosing schemes that maximize therapeutic benefit and minimize adverse events. Much of the information related to the effectiveness of dose modifications for targeted therapies in metastatic renal cell carcinoma has been gathered from clinical studies that have strict inclusion and exclusion criteria, which might not translate directly to real-world patient populations. This review discusses the impact of dose adherence on the effectiveness of targeted agents to treat metastatic renal cell carcinoma, assesses the literature regarding the effectiveness of approved dosing strategies, and provides a summary of alternative dosing strategies.