The drug inhibits a variety of tyrosine kinase receptors, such as the VEGF and PDGF receptor, which contributes, in part, to it's antitumoral activity. Reported toxicities include fatigue, hand-foot syndrome, and diarrhea, among others, although the drug is overall well tolerated with toxicities responsive to dose reductions and/or holidays. Because the RET proto-oncogene is also inhibited by sunitinib, these investigators from Dana Farber Cancer Institute evaluated thyroid function in GIST patients taking sunitinib.

In this study, 42 patients were treated for a median of 37 weeks (range 10-167 weeks) with sunitinib. Thyroid function studies were obtained prospectively during a clinical trial examining the activity of sunitinib, to look for evidence of thyroid dysfunction. Abnormal serum thyroid stimulating hormone (TSH) levels were noted in 62% of patients on sunitinib. Of these 36% developed persistent primary hypothyroidism, 10% developed isolated TSH suppression, and 17% experienced transient, mild TSH elevations. The investigators noted that the risk of hypothyroidism increased with the duration of sunitinib therapy and that 40% of hypothyroid patients had suppressed TSH levels prior to developing hypothyroidism, thus suggesting thyroiditis as a potential etiology of the hypothyroidism. Of note, two patients who developed hypothyroidism, with documented normal pre-therapy thyroid function, underwent thyroid ultrasound where no thyroid tissue was visualized, suggesting destruction and involution of the gland while on therapy.

The authors conclude that hypothyroidism is a common complication of sunitinib therapy that must be surveilled for in patients on therapy. While the mechanism remains unknown, the current study suggests that the drug may induce a destructive thyroiditis with follicular apoptosis. The authors also noted that this observation provided compelling evidence to consider evaluating the activity of sunitinib in advanced thyroid cancer.

Jayesh Desai, Leila Yassa, Ellen Marqusee, Suzanne George, Mary C. Frates, Ming Hui Chen, Jeffrey A. Morgan, Samuel S. Dychter, P. Reed Larsen, George D. Demetri, and Erik K. Alexander

Ann Internal Med 145(9): 660-664

UroToday.com articles on Sunitinib

UroToday.com Renal Cancer Section

Written by Christopher G. Wood, MD, a Contributing Editor with UroToday.

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