Endocrine Division, Thyroid Section, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Eur J Endocrinol. 2013 May 2;168(6):K51-4. doi: 10.1530/EJE-13-0015. Print 2013 Jun.
Medullary thyroid carcinoma (MTC) accounts for 3-4% of all malignant thyroid neoplasias. Vandetanib, a tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor 2, epidermal growth factor receptor, and RET, has been approved by the FDA for the treatment of locally advanced or metastatic MTC. The heart seems to be particularly susceptible to adverse effects associated with TKI therapy, and virtually all TKIs have been associated with cardiovascular events.
We report the case of a patient with metastatic MTC who was enrolled in the Phase III clinical study (NCT00410761) and presented a favorable response to vandetanib therapy, displaying marked decrease in the level of serologic tumor markers and shrinkage of metastatic lesions. After 14 months of therapy, the patient developed a fatal cardiac failure. Myocardial infarction was excluded by serial measurements of specific cardiac markers (serial troponin-T measurements varied from 0.037 to 0.042 ng/ml) and serologic tests for Chaga's disease were negative. Postmortem examination of the heart revealed cardiomyocyte hypertrophy and marked myocyte degeneration in the subendocardial zones and papillary muscles of the myocardium. These pathological changes are similar to those observed in TKI-treated rats and are suggestive of drug-induced cardiotoxicity.
This case illustrates a previously unreported serious vandetanib-related adverse effect and highlights the need for close monitoring of patients under TKI therapy in order to identify early signs of congestive heart failure or myocardium damage.
甲状腺髓样癌（MTC）占所有恶性甲状腺肿瘤的 3-4%。凡德他尼，一种针对血管内皮生长因子受体 2、表皮生长因子受体和 RET 的酪氨酸激酶抑制剂（TKI），已被 FDA 批准用于治疗局部晚期或转移性 MTC。心脏似乎特别容易受到与 TKI 治疗相关的不良反应的影响，几乎所有 TKI 都与心血管事件有关。
我们报告了一例转移性 MTC 患者的病例，该患者参加了 III 期临床试验（NCT00410761），对凡德他尼治疗有良好的反应，血清肿瘤标志物水平显著下降，转移性病变缩小。治疗 14 个月后，患者发生致命性心力衰竭。通过连续测量特定的心脏标志物（连续肌钙蛋白-T 测量值从 0.037 到 0.042ng/ml）和血清查加斯病检测排除了心肌梗死，并且心脏的尸检显示心肌细胞肥大和心肌下壁和心乳头肌的明显肌细胞变性。这些病理变化与在接受 TKI 治疗的大鼠中观察到的变化相似，提示药物引起的心脏毒性。
本病例说明了一种以前未报道的严重的凡德他尼相关不良反应，并强调了需要密切监测接受 TKI 治疗的患者，以识别充血性心力衰竭或心肌损伤的早期迹象。
