Phase II trial of saracatinib (AZD0530), an oral SRC-inhibitor for the treatment of patients with hormone receptor-negative metastatic breast cancer.
Phase II trial of saracatinib (AZD0530), an oral SRC-inhibitor for the treatment of patients with hormone receptor-negative metastatic breast cancer.
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DOI：
10.1016/j.clbc.2011.03.021
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发表时间：
2011-10
影响因子：
3.1
通讯作者：
Traina TA
中科院分区：
文献类型：
--
作者：
Gucalp A;Sparano JA;Caravelli J;Santamauro J;Patil S;Abbruzzi A;Pellegrino C;Bromberg J;Dang C;Theodoulou M;Massague J;Norton L;Hudis C;Traina TA
Src的激活与细胞迁移、增殖和转移有关。Saracatinib是一种对Src具有选择性的口服酪氨酸激酶抑制剂（TKI）。我们进行了这项试验，以评估Saracatinib单药治疗雌激素受体（ER）和孕激素受体（PR）阴性转移性乳腺癌患者的疗效和安全性。既往接受过≤1种可测量、ER和PR阴性转移性乳腺癌化疗方案的患者接受了saracatinib 175 mg每日一次口服给药。主要终点是疾病控制，定义为完全缓解（CR）+部分缓解（PR）+疾病稳定（SD）>6个月。次要终点包括毒性和无进展生存期。随着时间的推移，测量了循环肿瘤细胞对治疗的反应水平。9例患者在研究中接受治疗。中位2个周期（范围1-3）后，无患者达到CR、PR或SD >6个月。治疗失败的中位时间为82天（12-109）。大多数（89%）患者因疾病进展而停用saracatinib。1例患者发生了潜在治疗相关的4级缺氧伴间质浸润，并从研究中排除。常见的不良事件包括疲劳、肝化学升高、恶心、低钠血症、呼吸困难、咳嗽和肾上腺功能不全。这些疗效结果不足以证明本研究的持续招募是合理的。基于该系列，saracatinib似乎对治疗ER（−）/PR（−）转移性乳腺癌患者没有显著的单药活性。
Src activation is associated with cell migration, proliferation and metastasis. Saracatinib is an oral, tyrosine kinase inhibitor (TKI) selective for Src. We performed this trial to evaluate the efficacy and safety of saracatinib monotherapy in patients with estrogen receptor (ER)- and progesterone receptor (PR)-negative, metastatic breast cancer. Patients with ≤1 prior chemotherapy regimen for measurable, ER- and PR-negative metastatic breast cancer received saracatinib 175 mg orally daily. The primary endpoint was disease control defined as complete response (CR) + partial response (PR) + stable disease (SD) >6 months. Secondary endpoints included toxicity and progression-free survival. Levels of circulating tumor cells in response to therapy were measured over time. Nine patients were treated on study. After a median of 2 cycles (range 1–3), no patients achieved CR, PR, or SD >6 months. The median time to treatment failure was 82 days (12–109).The majority (89%) of patients discontinued saracatinib because of disease progression. One patient developed potentially treatment-related grade 4 hypoxia with interstitial infiltrates and was removed from study. Common adverse events included fatigue, elevated liver chemistries, nausea, hyponatremia, dyspnea, cough, and adrenal insufficiency. These efficacy results were not sufficiently promising to justify continued accrual to this study. Based on this series, saracatinib does not appear to have significant single-agent activity for the treatment of patients with ER(−)/PR(−) metastatic breast cancer.
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影响因子：
158.5
作者：
Cristofanilli, M;Budd, GT;Hayes, DF
通讯作者：
Hayes, DF
影响因子：
3.8
作者：
Hiscox, Stephen;Morgan, Liam;Nicholson, Robert I.
通讯作者：
Nicholson, Robert I.
影响因子：
45.3
作者：
Shah, Neil P.;Kantarjian, Hagop M.;Hochhaus, Andreas
通讯作者：
Hochhaus, Andreas
影响因子：
11.4
作者：
Hochhaus, A.;Baccarani, M.;Kantarjian, H. M.
通讯作者：
Kantarjian, H. M.
影响因子：
3.8
作者：
Ito, Y;Kawakatsu, H;Matsuura, N
通讯作者：
Matsuura, N