Kidney cancer. Principles and practice. Second edition. Primo N. Lara, Jr. Eric Jonasch (Editors). Springer International Publishing (2015)

Targeted therapies have significantly changed the treatment landscape for patients with metastatic renal cell carcinoma (mRCC). TKIs such as sunitinib, sorafenib, pazopanib, and axitinib are all multi-targeted inhibitors which inhibit a variety of targets including the vascular endothelial growth factor receptors 1, 2, and 3, platelet-derived growth factor receptor (PDGFR), and others [1–5]. Temsirolimus and everolimus both interfere with angiogenesis by inhibiting mTOR, a critical regulator within the cell [6, 7]. Bevacizumab blocks the vascular endothelial growth factor (VEGF) pathway by binding to VEGF [8].

It is now widely accepted that these targeted agents have a unique mechanism of action and are associated with a distinct and unique pattern of toxicities. While targeted agents generally have an acceptable toxicity profile, some side effects require careful monitoring and treatment in order to achieve optimal patient outcomes. In clinical practice, the most common side effects of targeted agents are fatigue/asthenia, anorexia/ loss of appetite, hand-foot syndrome (HFS) stomatitis/taste changes, diarrhea/abdominal pain, myelosuppression, and hypertension, while mTOR inhibition frequently is associated with mucocutaneous side effects, metabolic disturbances such as hyperglycemia and hyperlipidemia, and pneumonitis.

Three key interlinked areas have emerged as being essential for the optimal use of targeted agents in mRCC: dosing and schedule, treatment duration, and proactive side effect management. Only if all of these three key areas are optimized will the maximum benefit be achieved for each patient. Unlike conventional chemotherapy, targeted agents are given continuously as long as the patient benefits, which in some cases may extend for several years. This continuous treatment application makes side effect management critical and requires individualized management of the delicate balance between toxicity and dose intensity in order to maximize quality of life as well as patient benefit.

Knowledge about and optimal proactive management of acute side effects is therefore essential and may help to reduce patient discomfort and avoid unnecessary dose reductions, treatment interruptions, or even early treatment discontinuation. Patients undergoing treatment with targeted agents should be monitored by a qualified physician and/or oncology nurse experienced in the use of anticancer agents and should be counseled on the potential for treatment-related side effects, including the importance of maintaining optimal dose and therapy duration.

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