title: A phase 1B dose escalation trial of Scutellaria barbata (BZL101) for patients with metastatic breast cancer.
abstract: 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.
authors.affiliation: Memorial Cancer Institute, Hollywood, FL, USA.
authors.forename: Alejandra T
authors.initials: AT
authors.lastname: Perez
authors.forename: Banu
authors.initials: B
authors.lastname: Arun
authors.forename: Debu
authors.initials: D
authors.lastname: Tripathy
authors.forename: Mary A
authors.initials: MA
authors.lastname: Tagliaferri
authors.forename: Heather S
authors.initials: HS
authors.lastname: Shaw
authors.forename: Gretchen G
authors.initials: GG
authors.lastname: Kimmick
authors.forename: Isaac
authors.initials: I
authors.lastname: Cohen
authors.forename: Emma
authors.initials: E
authors.lastname: Shtivelman
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Caygill
authors.forename: Deborah
authors.initials: D
authors.lastname: Grady
authors.forename: Mark
authors.initials: M
authors.lastname: Schactman
authors.forename: Charles L
authors.initials: CL
authors.lastname: Shapiro
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000008:administration & dosage* / Q000009:adverse effects; D031363:Scutellaria
chemical_list: D000970:Antineoplastic Agents; D010936:Plant Extracts; C524947:Scutellaria barbata extract