Sunitinib in metastatic renal cell carcinoma: recommendations for management of noncardiovascular toxicities

Abstract

The multitargeted tyrosine-kinase inhibitor sunitinib has emerged as one of the standards of care for good- and intermediate-risk metastatic renal cell carcinoma. Although generally associated with acceptable toxicity, sunitinib exhibits a novel and distinct toxicity profile that requires monitoring and management. Fatigue, diarrhea, anorexia, oral changes, hand-foot syndrome and other skin toxicity, thyroid dysfunction, myelotoxicity, and hypertension seem to be the most common and clinically relevant toxicities of sunitinib. Drug dosing and treatment duration are correlated with response to treatment and survival. Treatment recommendations for hypertension have been published but, currently, no standard guidelines exist for the management of noncardiovascular side effects. To discuss the optimal management of noncardiovascular side effects, an international, interdisciplinary panel of experts gathered in November 2009. Existing literature on incidence, severity, and underlying mechanisms of side effects as well as on potential treatment options were carefully reviewed and discussed. On the basis of these proceedings and the thorough review of the existing literature, recommendations were made for the monitoring, prevention, and treatment of the most common noncardiovascular side effects and are summarized in this review. The proactive assessment and consistent and timely management of sunitinib-related side effects are critical to ensure optimal treatment benefit by allowing appropriate drug dosing and prolonged treatment periods.

Figure 1.

Incidence of fatigue/asthenia decreases over cycles in the phase III study (1034) and the expanded-access program (1037).

Figure 2.

Recommendations for fatigue management.

Figure 3.

Incidence of hypothyroidism by cycle in the phase III study (1034) and the expanded-access program (1037).

Figure 4.

Recommendations for thyroid dysfunction management.

Figure 5.

Incidence of hand-foot syndrome by cycle in the phase III study (1034) and the expanded-access program (1037).

Figure 6.

Recommendations for management of hand-foot syndrome.

Figure 7.

Incidence of oral toxicity by cycle in the phase III study (1034) and the expanded-access program (1037).