Objective: There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib,a novel multitargeted receptor tyrosine kinase inhibitor, has previously shown antitumor activity in phase Ⅱ studies of patients with advanced MTC. This study was to evaluate the efficacy and the safety of vandetanib on advanced MTC. Methods: This study was an open, international multi-center phase Ⅲ clinical trial and the study number was NCT01298323. The single-center study was a sub-group analysis of the international study, which was conducted on 9 pathologically confirmed advanced MTC patients by Cancer Hospital Chinese Academy of Medical Sciences between March 2012 and October 2017. Vandetanib (300 mg) was orally administered daily till death or withdrawal. The efficacy was evaluated according to RECIST criteria and the adverse events were evaluated according to NCI criteria. Results: The objective response rate was 3/9,and the disease control rate was 4/9. The median progression-free survival was 44 months. All patients who had the elevated levels of calcitonin (CTN) and carcino-embryonic antigen (CEA) before treatment began to show the decreases in the level of CTN and CEA after 3 months and later showed again the increases in the levels of both tumor markers with tumor progression. By ROC curve analysis, CTN was of statistically significance(P<0.05, 95%CI 0.558-0.834), but CEA was not(P>0.05). Adverse events were generally mild (grade 1 or 2),including hypertension (9 cases),skin rash (9 cases), and diarrhea (6 cases). Two patients developed grade 3 elevation of serum glutamate pyruvate transaminase and one patient developed grade 3 elevation of drug-related bowel disease. No grade 4 drug-related adverse event occurred. Conclusions: Vandetanib is effective and well tolerated for patients with locally advanced or metastatic MTC who have no chance for surgery. This indicates the increase of CTN is clinically relevant to disease progression, but the number of patients are extremely low, and, therefore further research is needed. Long-term use of vandetanib may cause resistance.
目的： 本研究旨在评价凡他尼布治疗晚期甲状腺髓样癌患者的疗效和安全性。 方法： 本研究为开放的、国际多中心Ⅲ期临床试验，研究编号为NCT01298323。本组资料为中国医学科学院北京协和医学院肿瘤医院2012年3月至2017年10月的单中心病例资料，共9例散发型甲状腺髓样癌患者，口服凡他尼布300 mg，每天1次顿服直至患者死亡或退出。采用RECIST实体瘤疗效评价标准评价疗效，毒性评价标准评价不良反应。 结果： 9例患者客观缓解比例为3/9，疾病控制比例为4/9，中位无进展生存期为44个月。在肿瘤标记物水平上，所有治疗前血清降钙素（calcitonin，CTN）及癌胚抗原（carcino-embryonic antigen，CEA）升高的患者均在服药3个月后开始下降，且随后再次升高的患者均出现疾病进展；经受试者工作特征曲线分析，CTN对诊断疾病进展有统计学意义（P<0.05，95%CI为0.558~0.834），而CEA对诊断进展没有统计学意义（P>0.05）。口服凡他尼布不良反应主要是高血压（9例次）、皮疹（9例次）及腹泻（6例次），多为1~2级。3级转氨酶升高2例，3级药物相关性肠病1例。未出现4级药物相关不良反应。 结论： 凡他尼布对失去手术机会的局部晚期或转移性甲状腺髓样癌患者短期内疗效显著，但长期使用可能会引起耐药。CTN升高可能预示肿瘤进展。在安全性上，患者对凡他尼布耐受性较好，但其不良反应较多，需密切随访。.
Keywords: Carcinoma, medullary; Drug resistance neoplasms; Targeted therapy; Thyroid neoplasms.