Phase I trial and antitumor effects of BZL101 for patients with advanced breast cancer. Breast Cancer Res Treat

University of California, San Francisco Carol Franc Buck Breast Care Center, San Francisco, USA.
Breast Cancer Research and Treatment (Impact Factor: 3.94). 09/2007; 105(1):17-28. DOI: 10.1007/s10549-006-9430-6
Source: PubMed


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.
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.
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.
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.

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    • "Kral [4] reported the appearance of S. racemosa in the southeast U.S. Ethnobotanical information suggests that the Cauca people of Columbia and Ecuador used certain ecotypes of S. racemosa in ceremonial or sedative preparations [5]. S. barbata has been tested in two clinical trials for the treatment of advanced and metastatic breast cancer with positive results [6] [7]. Laboratory studies using Barbat skullcap extracts have shown to induce apoptosis in prostate cancer, and hepatoma H22 cells [8]-[10]. "
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    • "Thus, strategies targeting AIF-mediated caspase-independent cell death have been applied as a therapeutic treatment for cancers. For example, a plant drug from Scutellaria barbatae that stimulates AIF translocation from the mitochondria to the nucleus showed anti-tumor effects in breast cancer patients [24]. Since cathepsin release from lysosomes regulates the AIF-mediated cell death pathway and several members of the cathepsin family have been implicated in cancer progression and metastasis [25], [26], cathepsin is a potential target to modulate caspase-independent cell death for cancer treatment. "
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    • "S. barbata extract was shown to have cytotoxic activity against various tumor cell lines in vitro [1], [2], [3], [4], [5], [6], [7], [8], [9], [10] and antitumor activity in vivo [11], [12], [13] in models of renal, hepatocellular and prostate carcinoma. More importantly, two early stage clinical trials with Bezielle showed promising efficacy and excellent safety for treatment of advanced breast cancer [14], [15]. In the phase Ia clinical trial sixteen patients, all of which went through multiple treatment therapies prior to enrollment were evaluable for response. "
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