Thyroid function test (TFT) abnormalities in patients (pts) with metastatic renal cell carcinoma (RCC) treated with sorafenib

Abstract

5048 Background: Sorafenib is an orally bioavailable VEGF receptor inhibitor with anti-tumor activity in metastatic RCC. Sunitinib, another VEGF receptor inhibitor, induces biochemical hypothyroidism in 85% of metastatic RCC pts, the majority of whom have signs or symptoms of hypothyroidism (Rini BI et al. JNCI 2007 99(1):81–83). Thus, the incidence of TFT abnormalities in pts with metastatic RCC receiving sorafenib was investigated. Methods: The medical records of pts with metastatic RCC receiving sorafenib in one of five clinical trials at the Cleveland Clinic Taussig Cancer Center were reviewed. TFTs (TSH, T4, FTI and T3), patient demographics and clinical outcomes were recorded. Results: Between February 2004 and November 2006, 71 pts (49 males, 22 females) were treated with sorafenib. Baseline pt characteristics included a median age of 62 years (range, 35–87), 87% of pts had clear cell histology and 97% had prior nephrectomy. Forty-two pts had TFTs measured while receiving sorafenib and 19/42 pts (45%; 95% CI: 30–61%) had abnormal TFTs. The TFT abnormalities were consistent with hypothyroidism (13 pts), euthyroid sick syndrome (2 pts) or hyperthyroidism (4 pts). The median values in pts with abnormal TFTs were: TSH-7 μU/ml, T3–79 ng/dl, T4–12.7 μg/dl, FTI- 5.4; these values are just outside the normal laboratory ranges. The majority of pts did not have clinical signs or symptoms that could be attributed solely to thyroid dysfunction; only one pt (2%) received thyroid hormone replacement. The estimated progression free survival for pts with normal TFTs is 7.5 months vs. 6.1 months for pts with abnormal TFTs (p=0.79). Conclusion: Mild biochemical TFTs abnormalities are common in pts with metastatic RCC treated with sorafenib. However, severe TFT abnormalities and/or clinical signs/symptoms of thyroid dysfunction are not seen, and thyroid replacement therapy is not often indicated. In contrast to sunitinib, where the high incidence and clinical relevance of thyroid dysfunction requires routine monitoring, pts with metastatic RCC receiving sorafenib should have TFTs monitored only if clinically indicated. [Table: see text]