Sunitinib therapy for metastatic renal cell carcinoma: recommendations for management of side effects
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abstract
Sunitinib, a new vascular endothelial growth factor receptor inhibitor, has demonstrated high activity in renal cell carcinoma (RCC) and is now widelyused for patients with metastatic disease. Although generally well tolerated andassociated with a low incidence of common toxicity criteria grade 3 or 4 toxicities, sunitinib exhibits a distinct pattern of novel side effects that require monitoring and management. This article summarizes the most important side effects and proposes recommendations for their monitoring, prevention and treatment,based on the existing literature and on suggestions made by an expert groupof Canadian oncologists. Fatigue, diarrhea, anorexia, oral changes, skin toxicityand hypertension seem to be the most clinically relevant toxicities of sunitinib. Fatigue may be partly related to the development of hypothyroidismduring sunitinib therapy for which patients should be observed and, if necessary, treated. Hypertension can be treated with standard antihypertensivetherapy and rarely requires treatment discontinuation. Neutropenia and thrombocytopenia usually do not require intervention, in particular no episodes ofneutropenic fever have been reported to date. A decrease in left ventricula rejection fraction is a rare, but potentially life-threatening side effect. Becauseof its metabolism by cytochrome P450 3A4 a number of drugs can potentiallyinteract with sunitinib. Clinical response and toxicity should be carefullyobserved when sunitinib is combined with either a cytochrome P450 3A4 induceror inhibitor and doses adjusted as necessary. Knowledge about side effects, as well as the proactive assessment and consistent management of sunitinib related side effects, is critical to ensure optimal benefit from sunitinib treatment.
