Sunitinib therapy for metastatic renal cell carcinoma: recommendations for management of side effects

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.

Hypertension Management in Patients with Renal Cell Cancer Treated with Anti-Angiogenic Agents

“…Thus, there is no evidence that mrcc patients should be treated differently than other hypertensive patients; however, the potential for interactions between antihypertensives (which inhibit the cytochrome P450 system) and vegfis should be taken into consideration. The vegf-is such as sunitinib are metabolized in the liver by cytochrome P450 3A4, and inhibitors of that isoenzyme such as diltiazem or verapamil should be avoided 32 .…”

Two Side Effects of Sutent Therapy in Renal Cell Carcinoma: A Case Report

“…However, some distinct side effects require monitoring and treatment. Because of the metabolism and mode of action of sunitinib and the distinct pattern of toxicity, the management of side effects becomes an important issue (5). We have decreased the dosage of drug from 50 mg to 12.5 mg four weeks on and two weeks off the severity of side effect decreased.…”

Oral Adverse Events Associated with Tyrosine Kinase and Mammalian Target of Rapamycin Inhibitors in Renal Cell Carcinoma: A Structured Literature Review

“…Interestingly, and also unlike oral mucosal toxicity associated with conventional chemotherapy, patients on such targeted agents may sometimes present with oral complaints such as mouth pain, dysgeusia, and dysphagia in the absence of any clinically apparent lesion [14,21,32]. Such symptoms have been reported to rapidly improve during treatment-free intervals [23] and may occur again with additional dosing of the targeted agent.…”

“…For example, sunitinib treatment has been associated with oral mucosal hypersensitivity, oral ulcers, cheilitis, and taste alterations [23,31]. Oral lesions associated with mTORIs have been described as discrete, oval, superficial ulcers with an erythematous halo (Fig.…”

“…1). Pain, dysesthesia, erythema, and edema [21,22] are common symptoms on mechanically strained regions and can even appear without obvious skin alterations [23].…”