高剂量他莫昔芬用于高激素受体表达的晚期乳腺癌患者：一项II期试点研究。
High-dose tamoxifen in high-hormone-receptor-expressing advanced breast cancer patients: a phase II pilot study.
作者信息
Su Yanhong, Zhang Yarui, Hua Xin, Huang Jiajia, Bi Xiwen, Xia Wen, Wang Xinyue, Huang Zhangzan, Song Chenge, Zhong Yongyi, Shi Yanxia, Wang Shusen, Fan Wei, Yuan Zhongyu
机构信息
Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.
Department of Nuclear Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
出版信息
Ther Adv Med Oncol. 2021 Feb 26;13:1758835921993436. doi: 10.1177/1758835921993436. eCollection 2021.
BACKGROUND
Tumor progression following endocrine therapy is considered to indicate resistance to endocrine drugs due to a variety of mechanisms. An insufficient dose of endocrine drugs is one of the causes for treatment failure in some patients with high hormone-receptor (HR)-expressing advanced breast cancer. This study aimed to explore the efficacy of high-dose tamoxifen (TAM) treatment in patients with advanced breast cancer with highly expressed HR.
MATERIALS & METHODS: This was a single-arm, phase II pilot study that enrolled patients with advanced breast cancer with high HR expression (estrogen receptor ⩾60% and/or progesterone receptor ⩾60%) following routine endocrine therapy. All enrolled patients received a high-dose of TAM (100 mg/day) until disease progression. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and safety. Exploratory endpoints included the predictive value of α-F-β-fluoroestradiol quantitative positron emission tomography/computed tomography (F-FES PET/CT) for treatment efficacy.
RESULTS
A total of 30 patients were enrolled between September 2017 and February 2019. The median PFS was 6 months [95% confidence interval (CI) 4.9-7.1] and the median OS was 15.6 months (95% CI 8.3-22.9). Five patients experienced a partial response (PR) and none experienced a complete response (CR), with an ORR of 16.7% and CBR of 33.3%. No severe adverse events were observed. Lesions with F-FES maximum standardized uptake value (SUVmax) ⩾4 had a significantly longer PFS [median 9.2 months, (95% CI 6.9-11.6)] compared with lesions with a F-FES SUVmax <4 [median 4.8 months, (95% CI 3.9-5.6); = 0.022].
CONCLUSION
A high-dose of TAM is effective and safe for patients with advanced breast cancer with high HR expression. F-FES SUVmax values may predict the local clinical benefits of high-dose TAM .
TRIAL REGISTRATION
[ClinicalTrials.gov identifier: NCT0304565].
背景
内分泌治疗后肿瘤进展被认为是由于多种机制导致对内分泌药物产生耐药。内分泌药物剂量不足是部分激素受体（HR）高表达的晚期乳腺癌患者治疗失败的原因之一。本研究旨在探讨大剂量他莫昔芬（TAM）治疗HR高表达的晚期乳腺癌患者的疗效。
材料与方法
这是一项单臂II期试验性研究，纳入常规内分泌治疗后HR高表达（雌激素受体⩾60%和/或孕激素受体⩾60%）的晚期乳腺癌患者。所有入组患者接受大剂量TAM（100mg/天）治疗直至疾病进展。主要终点为无进展生存期（PFS）。次要终点包括客观缓解率（ORR）、临床获益率（CBR）、总生存期（OS）和安全性。探索性终点包括α-F-β-氟雌二醇定量正电子发射断层扫描/计算机断层扫描（F-FES PET/CT）对治疗疗效的预测价值。
结果
2017年9月至2019年2月共纳入30例患者。中位PFS为6个月[95%置信区间（CI）4.9 - 7.1]，中位OS为15.6个月（95%CI 8.3 - 22.9）。5例患者出现部分缓解（PR），无完全缓解（CR），ORR为16.7%，CBR为33.3%。未观察到严重不良事件。F-FES最大标准化摄取值（SUVmax）⩾4的病灶PFS显著长于F-FES SUVmax<4的病灶[中位9.2个月，（95%CI 6.9 - 11.6）]，而F-FES SUVmax<4的病灶中位为4.8个月，（95%CI 3.9 - 5.6）；P = 0.022]。
结论
大剂量TAM治疗HR高表达的晚期乳腺癌患者有效且安全。F-FES SUVmax值可能预测大剂量TAM的局部临床获益。
试验注册
[ClinicalTrials.gov标识符：NCT0304565]
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