Understanding and managing toxicities of vascular endothelial growth factor (VEGF) inhibitors

Vascular-endothelial growth-factor (receptor) (VEGF)(R)-inhibiting agents – sunitinib [1–3], sorafenib [4,5], pazopanib [2,6], bevacizumab [7,8], axitinib [5] and tivozanib [9,10] – have changed the therapeutic landscape in metastatic renal-cell carcinoma (mRCC). Five out of six agents have been approved for either first-line (sunitinib, pazopanib and bevacizumab + interferon-alpha) or second-line (sorafenib, axitinib) treatment of metastatic or advanced RCC. With these novel strategies, the median overall survival of patients has increased considerably, often, however, at the expense of chronic side-effects. Common treatment-related side-effects include: (1) general symptoms such as fatigue and asthenia, (2) gastrointestinal symptoms such as diarrhoea and stomatitis, (3) skin toxicities, (4) cardiovascular toxicities and (5) a variety of laboratory abnormalities. Some of these side-effects are clinically highly relevant because they may jeopardise the patient’s safety or quality of life, while others may have little clinical relevance. Treating physicians need to be aware of potential side-effects that may occur, how to prevent and/or manage them, and the clinical implications for the ongoing treatment. This is of paramount importance since dose reductions and treatment discontinuations may significantly affect the outcome [11].