医学
曲美替尼
达布拉芬尼
甲状腺癌
内科学
甲状腺癌
不利影响
癌症
胃肠病学
肿瘤科
中性粒细胞减少症
甲状腺
癌症研究
威罗菲尼
化疗
MAPK/ERK通路
激酶
生物
转移性黑色素瘤
细胞生物学
作者
Gerald S. Falchook,Michael Weichenthal,David S. Hong,Aung Naing,Sarina A. Piha‐Paul,Steven G. Waguespack,Maria E. Cabanillas,Steven I. Sherman,Bo Ma,Martin Curtis,Vicki Goodman,Razelle Kurzrock
出处
期刊:Thyroid
[Mary Ann Liebert]
日期:2015-01-01
卷期号:25 (1): 71-77
被引量:198
标识
DOI:10.1089/thy.2014.0123
摘要
Background: Mutations of v-raf murine sarcoma viral oncogene homolog B (BRAF) are commonly identified in papillary and anaplastic thyroid carcinoma and are associated with worse prognosis compared with the wild type. BRAF inhibition in papillary thyroid carcinoma cell lines and xenografts inhibits proliferation and decreases downstream phosphorylation. Our objectives were to analyze safety and efficacy of the selective BRAF inhibitor dabrafenib in patients with metastatic BRAF-mutant thyroid carcinoma. Methods: We present the subset of patients with BRAF-mutant thyroid carcinoma enrolled in a larger phase 1 study, the main results of which are reported elsewhere. Results: Fourteen patients with BRAFV600E-mutant thyroid carcinoma were enrolled, of whom 13 (93%) had received prior radioactive iodine. The median duration on treatment was 8.4 months, and seven (50%) patients received treatment for ≥10 months. The most common treatment-related adverse events were skin papillomas (n=8, 57%), hyperkeratosis (n=5, 36%), and alopecia (n=4, 29%), all of which were grade 1. Treatment-related adverse events grade ≥3 included grade 4 elevated lipase and grade 3 elevated amylase, fatigue, febrile neutropenia, and cutaneous squamous cell carcinoma (n=1 for each). Four (29%) partial responses were observed, and nine (64%) patients achieved at least 10% decrease. Only one responder progressed while on the study drug after a response duration of 9.3 months. The other three responders had not progressed, with response duration of 4.6+, 10.4+, and 21.4+ months. With seven (50%) patients showing no progression at the time of study completion, the median progression-free survival was 11.3 months. Conclusions: Dabrafenib was well tolerated and resulted in durable responses in BRAF-mutant differentiated thyroid carcinoma patients.
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