小分子VEGFR-TKI治疗晚期肾透明细胞癌致甲状腺功能减低研究

Study on hypothyroidism caused by treating metastatic clear cell renal cell carcinoma with small molecule VEGFR-TKI

目的探讨小分子第二代血管内皮生长因子受体抑制剂(vascular endothelial growth factor receptor tyrosine kinase inhibitor,VEGFR-TKI)治疗晚期肾透明细胞癌致甲状腺功能减低的发生及其疗效。方法对2009年11月~2010年12月本院收治的24例晚期肾透明细胞癌患者,其中索拉非尼或阿昔替尼组10例,对照组(细胞因子)14例。分析甲状腺功能指标的变化趋势及其预后。结果 TKI组甲减的发生率50.0%,高于对照组甲减发生率7.1%(X^2=5.714,P=0.017)。甲减发生的中位生存时间56.2个月,甲功检测表现为促甲状腺激素明显升高伴血清游离甲状腺素(free thyroxine,FT4)同步下降,但游离三碘甲状腺原氨酸(free triiodothyronine,FT3)下降时间较为滞后。TKI组和对照组中位生存时间分别为:21.0个月(95%CI:0.001~54.200)和15.0个月(95%CI:4.000~26.000;P=0.265)。结论小分子VEGFR-TKI治疗晚期转移性肾透明癌,TKI组甲减的发生率较对照组升高,生存时间较长。甲减可能是较常见的毒副反应,甲状腺功能的长期监测和甲减的适时干预,有助于提高患者治疗依从性和改善生存质量。

Objective To investigate the incidence of hypothyroidism and efficacy of metastatic clear cell renal cell carcinoma treated with small molecule VEGFR-TKI. Methods A retrospective study was conducted to analyze the clinical data of 24 patients treated with TKI （Axitinib or Sorafenib） therapy（ n = 10） or cytokine therapy （n = 14） from No- vember 2009 to December 2010. The change trend of thyroid function index and prognosis between TKI group and control group were analyzed. Results TKI group with hypothyroidism was higher than control group （50. 0% vs. 7.1%, %2 = 5. 714, P = 0. 017）. The median time of hypothyroidism was 56. 2 months, thyroid stimulating hormone （TSH） increased obviously, free thyroxine （Fr4） decreased synchronously and free triiodothyronine （Fl＇3） fall time was relatively lagging behind in TKI group. The median overall survival was 21 （95% CI：O. 001-54. 200） months of TKI group versus 15 （95% CI：4. 000-26. 000） months of control group （P = 0. 265）. Conclusions The incidence of hypothyroidism of TKI group is significantly higher than the control group, the survival time is longer. The hypothyroidism is a common side effect of meta- static clear cell renal carcinoma patients receiving small molecule VEGFR-TKI. Long term monitoring thyroid function and timely intervention of hypothyroidism can improve the patient＇s treatment compliance and quality of life.