Phase I trial and antitumor effects of BZL101 for patients with advanced breast cancer

Breast Cancer Res Treat. 2007 Sep;105(1):17-28. doi: 10.1007/s10549-006-9430-6. Epub 2006 Nov 17.

Abstract

Background: Botanical therapies are often used by breast cancer patients yet few clinical trials have evaluated their safety and efficacy. We studied mechanisms of activity and performed a phase I clinical trial in patients with advanced breast cancer to evaluate BZL101, an aqueous extract from Scutellaria barbata.

Methods: Preclinical studies were conducted in vitro to characterize cell death induced by BZL101. In a phase I trial, eligible patients had histologically confirmed, measurable metastatic breast cancer. Treatment consisted of 350 ml per day of oral BZL101, administered as sole cancer therapy until disease progression, toxicity or personal preference to discontinue. Primary endpoints were safety, toxicity and tumor response.

Results: BZL101 extract induced strong growth inhibition and apoptosis of breast cancer cell lines. In the phase I trial, 21 patients received BZL101. Mean age was 54 years (30-77) and mean number of prior treatments for metastatic disease was 3.9 (0-10). There were no grade III or IV adverse events (AEs). The most frequently reported BZL101-related grade I and II AEs included: nausea (38%), diarrhea (24%), headache (19%) flatulence (14%), vomiting (10%), constipation (10%), and fatigue (10%). Sixteen patients were evaluable for response. Four patients had stable disease (SD) for >90 days (25%) and 3/16 had SD for >180 days (19%). Five patients had objective tumor regression, one of which was 1 mm short of a PR based on RECIST criteria.

Conclusions: BZL 101 inhibits breast cancer cell lines by inducing apoptosis. In a phase I clinical trial, BZL101 was safe and had a favorable toxicity profile. BZL101 demonstrated encouraging clinical activity in this heavily pretreated population.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Breast Neoplasms / drug therapy*
  • Caspases / metabolism
  • Cell Line, Tumor
  • DNA Fragmentation
  • Enzyme Activation
  • Female
  • Flow Cytometry / methods
  • Humans
  • Middle Aged
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Scutellaria / metabolism

Substances

  • Antineoplastic Agents
  • Plant Extracts
  • Scutellaria barbata extract
  • Caspases