Management of sunitinib adverse events in renal cell carcinoma patients: The Asian experience

Abstract

Sunitinib is the gold standard of care for patients with metastatic renal cell carcinoma, demonstrating an overall survival benefit of over 2 years in a pivotal phase 3 trial of 750 patients. While sunitinib is generally well tolerated with most adverse events, manifesting as mild to moderate in severity and manageability, it has a distinctive adverse event profile that benefits from careful monitoring during treatment. As sunitinib gains widespread use across the globe, best practices are being developed for specific patient groups. This review will focus on the current clinical trial data in Asian populations and on the mechanism, incidence and management of selected sunitinib-related adverse events, including hand-foot syndrome, hypertension, proteinuria, cardiac toxicities, myelosupression, fatigue/asthenia, hypothyroidism, diarrhea and hepatotoxicity. Taken together, the developing body of literature reviewed here demonstrates that sunitinib is well tolerated in Asian patients and provides efficacy that is similar, if not superior, to other patient groups. Asian patients, like all patients, should begin treatment of sunitinib at 50 mg on Schedule 4/2 (4 weeks on treatment/2 weeks off). Prophylactic measures, good communication between patient and health-care providers, and early, aggressive intervention at the development of adverse events can limit the dose reductions required and maximize both patients' response to treatment and their quality of life.

Sunitinib dosing schedule 2/1 improves tolerability, efficacy, and health-related quality of life in Chinese patients with metastatic renal cell carcinoma

“…HFS has previously been reported to be more common in Asians than in Western patients [10]. Although the incidence of grades 3 to 4 AEs showed no significant differences among the 3 treatment groups, the total incidences of HFS, fatigue, neutropenia, and diarrhea were significantly lower in the schedule I2/1 and T2/1 groups than in the schedule 4/2.…”

“…Currently, sunitinib 50 mg daily for 4 weeks followed by 2-weeks-off therapy (schedule 4/2) is recommended as the standard dosing schedule globally [9]. However, adverse events (AEs) associated with sunitinib should be strictly monitored including hypertension, handfoot syndrome (HFS), proteinuria, cardiac toxicity, bone marrow suppression, fatigue, diarrhea, hypothyroidism, and hepatotoxicity [10], as they result in poor tolerance of the drug and a relatively diminished health-related quality of life (HRQoL). Consequently, a sunitinib dosing schedule of 2 weeks on and 1 week off (schedule 2/1) is increasingly being used as an alternative regimen for reducing the incidence of AEs while achieving a comparable oncological outcome to the traditional schedule 4/2 [11][12][13].…”

Risks associated with sunitinib use and monitoring to improve patient outcomes

“…The use of VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs) is a major step forward in the treatment of several malignancies and has improved patient outcomes significantly [2]. The U.S. Food and Drug Administration (FDA) has approved four VEGF TKIs for use in cancer therapy: sunitinib (Sutent, Pf izer, New York, NY, USA), sorafenib (Nexavar, Bayer Pharmaceuticals, West Haven, CT, USA; and Onyx Pharmaceuticals, Richmond, CA, USA), pazopanib (Votrient, GlaxoSmithKline, Middlesex, UK), and vandetanib (Caprelsa, AstraZeneca, London, UK).…”

“…No sunitinib-specific guidelines exist for managing patients zof sunitinib is recommended in patients with urinary protein levels > 3 g in a 24-hour period. Sunitinib treatment can be restarted when the urinary protein level falls below this level [2]. …”

“…Cardiovascular events reported in patients on sunitinib therapy include heart failure, myocardial disorders, and cardiomyopathy [2]. Platelet-derived growth factor receptors (PDGFRs) are expressed on cardiomyocytes, and their overexpression can signal survival.…”