Clinical Division of Oncology, Department of Medicine I and Cancer Center, Medical University of Vienna, Vienna, Austria.
Cancer. 2011 Feb 1;117(3):534-44. doi: 10.1002/cncr.25422. Epub 2010 Sep 15.
Sunitinib and sorafenib are tyrosine kinase inhibitors that have important antitumor activity in metastatic renal cell carcinoma (mRCC). Hypothyroidism constitutes a commonly reported side effect of both drugs, and particularly of sunitinib. The objective of this analysis was to investigate whether the occurrence of hypothyroidism during treatment with sunitinib and sorafenib affects the outcome of patients with mRCC.
Eighty-seven consecutive patients with mRCC who were to receive treatment with sunitinib or sorafenib were included in a prospective analysis. Thyroid function was assessed in each patient every 4 weeks during the first 2 months of treatment and every 2 to 4 months thereafter. Assessment included serum levels of thyroid-stimulating hormone (TSH), tri-iodthyronine (T3), and thyroxine (T4). Subclinical hypothyroidism was defined as an increase in TSH above the upper limit of normal (>3.77 μM/mL) with normal T3 and T4 levels.
Subclinical hypothyroidism was evident in 5 patients at baseline and occurred in 30 patients (36.1%) within the first 2 months after treatment initiation. There was a statistically significant correlation between the occurrence of subclinical hypothyroidism during treatment and the rate of objective remission (hypothyroid patients vs euthyroid patients: 28.3% vs 3.3%, respectively; P < .001) and the median duration of survival (not reached vs 13.9 months, respectively; hazard ratio, 0.35; 95% confidence interval, 0.14-0.85; P = .016). In multivariate analysis, the development of subclinical hypothyroidism was identified as an independent predictor of survival (hazard ratio, 0.31; P = .014).
The current results indicated that hypothyroidism may serve as a predictive marker of treatment outcome in patients with mRCC. Thus, the interpretation of hypothyroidism during treatment with sunitinib and sorafenib as an unwanted side effect should be reconsidered.
舒尼替尼和索拉非尼是酪氨酸激酶抑制剂，在转移性肾细胞癌（mRCC）中具有重要的抗肿瘤活性。甲状腺功能减退是这两种药物（尤其是舒尼替尼）常见的报告副作用。本分析的目的是研究舒尼替尼和索拉非尼治疗期间甲状腺功能减退的发生是否影响 mRCC 患者的结局。
87 例连续 mRCC 患者接受舒尼替尼或索拉非尼治疗，纳入前瞻性分析。治疗的前 2 个月，每 4 周评估每位患者的甲状腺功能，此后每 2-4 个月评估一次。评估包括血清促甲状腺激素（TSH）、三碘甲状腺原氨酸（T3）和甲状腺素（T4）水平。亚临床甲状腺功能减退定义为 TSH 水平高于正常上限（>3.77 μM/mL），同时 T3 和 T4 水平正常。
基线时有 5 例患者存在亚临床甲状腺功能减退，治疗开始后 2 个月内有 30 例（36.1%）患者出现。治疗期间发生亚临床甲状腺功能减退与客观缓解率之间存在统计学显著相关性（亚临床甲状腺功能减退患者 vs 甲状腺功能正常患者：分别为 28.3% vs 3.3%；P<0.001）和中位生存时间（未达到 vs 13.9 个月，分别；危险比，0.35；95%置信区间，0.14-0.85；P=0.016）。多变量分析显示，亚临床甲状腺功能减退的发生是生存的独立预测因素（危险比，0.31；P=0.014）。
目前的结果表明，甲状腺功能减退可能是 mRCC 患者治疗结局的预测标志物。因此，在治疗期间将舒尼替尼和索拉非尼引起的甲状腺功能减退解释为不良副作用应该重新考虑。
