Efficacy and safety of vandetanib on advanced medullary thyroid carcinoma: single center result from a phase Ⅲ study
10.3760/cma.j.issn.1673-0860.2019.06.008
- VernacularTitle: 凡他尼布治疗晚期甲状腺髓样癌的临床疗效及安全性分析：Ⅲ期单中心研究结果
- Author:
Shixu WANG
1
;
Xiwei ZHANG
2
;
Xiaoxin WANG
3
;
Changming AN
2
;
Yabing ZHANG
4
;
Wan LIU
2
;
Yanfeng ZHAO
5
;
Xiaohui HE
6
;
Zhengjiang LI
2
;
Lijuan NIU
7
;
Pingzhang TANG
2
Author Information
1. Department of Head and Neck Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China
2. Department of Head and Neck Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
3. Department of Rehabilitation Medicine, Meitan General Hospital, Beijing 100028, China
4. Department of Head and Neck Surgery, Beijing Cancer Hospital/Beijing Institute for Cancer Research, Beijing 100142, China
5. Department of Image Diagnosis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
6. Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
7. Department of Ultrasound Diagnosis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- Publication Type:Journal Article
- Keywords:
Thyroid neoplasms;
Carcinoma, medullary;
Targeted therapy;
Drug resistance neoplasms
- From:
Chinese Journal of Otorhinolaryngology Head and Neck Surgery
2019;54(6):439-444
- CountryChina
- Language:Chinese
-
Abstract:
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.
