Efficacy and thyroidal effects of sunitinib in Japanese patients with metastatic renal cell carcinoma: Hypothyroidism and thyroid atrophy as potential biomarkers for sunitinib?

Abstract

e16097 Background: Although hypothyroidism is a well-known adverse effect of sunitinib in western patients (pts) with metastatic renal cell carcinoma (MRCC), the effects on thyroid gland of sunitinib in Japanese pts still remain unclear. We therefore evaluated thyroid dysfunction and thyroid atrophy in Japanese RCC pts who received sunitinib. Methods: Fourteen (8 males, 6 females) of 51 pts who were treated in a phase II trial of sunitinib in Japanese pts with MRCC were included in this retrospective study. All 14 pts were euthyroid at baseline. The measurement of serum thyroid function test (fT3, fT4, TSH) was performed at the beginning of each sunitinib treatment cycle. A TSH concentration greater than 10 mU/L was considered as hypothyroidism regardless of subclinical or clinical. CT volumetry of the thyroid gland was performed utilizing the data obtained for tumor assessment in a phase II trial. Tumor response was evaluated based on the RECIST criteria. Results: 9 (64%) of 14 pts achieved RECIST-defined objective response (1 CR, 8 PRs). With regard to thyroid function, hypothyroidism was experienced by 11 (79%) pts. Three of 11 pts had Sunitinib-induced thyrotoxicosis before experiencing hypothyroidism. The mean time to development of hypothyroidism was 55 days (range 13–668). Six pts received typical doses of L-thyroxine. The response rate was 73% (8/11) in pts with hypothyroidism and 33% (1/3) in pts without. With regard to the volume of thyroid gland in 13 pts, 8 pts had more than 50% reduction comparing the volume at the baseline. Median reduction rate in volume of 13 pts was 57% (range 0–95%). Hypothyroidism was experienced by all 8 pts with more than 50% reduction in volume and 2 of 5 (40%) without. Furthermore, the response rate was 88% (7/8) in former pts and 40% (2/5) in latter pts. Conclusions: In addition to high anti-tumor efficacy, hypothyroidism and thyroid atrophy were commonly observed in Japanese MRCC pts who received sunitinib. Although further study should be required, these abnormal findings in thyroid gland following treatment with sunitinib may be potential biomarkers for tumor response to sunitinib. [Table: see text]