A phase 1B dose escalation trial of Scutellaria barbata (BZL101) for patients with metastatic breast cancer
A phase 1B dose escalation trial of Scutellaria barbata (BZL101) for patients with metastatic breast cancer
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DOI：
10.1007/s10549-009-0678-5
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发表时间：
2010-02-01
影响因子：
3.8
通讯作者：
Shapiro, Charles L.
中科院分区：
文献类型：
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作者：
Perez, Alejandra T.;Arun, Banu;Shapiro, Charles L.
本研究的目的是确定BZL101(FDA IND#59,521)的安全性和最大耐受量(MTD)，BZL101是一种口服半枝莲水提取物，用于治疗转移性乳腺癌(MBC)。这是一项开放标签、1B期、多中心、剂量递增的研究。符合条件的患者有组织学确诊的乳腺癌和可测量的IV期疾病。采用标准的1期“3+3”研究设计来确定MTD。主要终点是BZL101的毒性和MTD。次要结果包括基于RECIST标准的疗效。共有27名女性接受了四个不同剂量的队列治疗，这些女性之前接受过两次化疗，治疗过的是转移性疾病。3级和4级不良事件并不常见。剂量限制毒性包括：4级AST升高，3级腹泻，3级乏力和3级肋骨疼痛。14例患者可根据实体瘤疗效评价标准进行评价。调查者评估将3名病情稳定的患者归类为120天(21%)。1例患者服用BZL101 449天，并保持稳定700多天。独立的放射学回顾发现有3名患者肿瘤目标消退(0%和30%)。未达到MTD，因此根据方案，MTD被定义为BZL101每天40g的最大给药剂量。总而言之，口服BZL101是安全的，耐受性良好，并显示出在这一经过大量预处理的MBC女性人群中具有抗癌活性的有希望的临床证据。
The purpose of this study was to determine the safety and maximum tolerated dose (MTD) of BZL101 (FDA IND# 59,521), an orally delivered aqueous extract from the herb Scutellaria barbata, in women with metastatic breast cancer (MBC). The trial was an open-label, phase 1B, multicenter, dose escalation study. Eligible patients had histologically confirmed breast cancer and measurable stage IV disease. The standard phase 1 "3 + 3" study design was used to determine the MTD. Primary endpoints were toxicity and MTD of BZL101. Secondary outcomes included efficacy based on RECIST criteria. A total of 27 women with a median of 2 prior chemotherapy treatments for metastatic disease were treated in four different dose cohorts. Grade 3 and 4 adverse events (AEs) were uncommon. Dose-limiting toxicities included the following: grade 4 AST elevation, grade 3 diarrhea, grade 3 fatigue, and grade 3 rib pain. Fourteen patients were evaluable according to Response Evaluation Criteria in Solid Tumors. Investigator assessment classified three patients with stable disease for > 120 days (21%). One patient was on BZL101 for 449 days and remains stable for 700 + days. Independent radiology review identified three patients with objective tumor regression (> 0% and < 30%). The MTD was not reached, thus per protocol, the MTD was defined as the maximum administered dose of BZL101 40 g/day. In conclusion, oral administration of BZL101 was safe, well tolerated, and showed promising clinical evidence of anticancer activity in this heavily pretreated population of women with MBC.