from UCSF--preclinical efficacy (with her2+ cell lines) and phaseI going on phase II

[Lani]

of BZL101, an aqueous extract from Scutellaria barbata.


Hope Rugo1, Emma Shtivelman2, Alejandra Perez3, Charles Vogel4, Sandra Franco3, Elizabeth Tan Chiu4, Michelle Melisko1, Mary Tagliaferri2, Isaac Cohen2, Mark Shoemaker2, Zung Tran5 and Debu Tripathy6, 7

(1) University of California, San Francisco Carol Franc Buck Breast Care Center, San Francisco, USA
(2) Bionovo, Inc., California, USA
(3) Regional Memorial Hospital, Hollywood, FL, USA
(4) Cancer Research Network, Plantation, FL, USA
(5) University of Colorado Health Sciences Center, Denver, CO, USA
(6) University of Texas Southwestern Medical Center, Dallas, TX, USA
(7) Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-8852, USA
Received: 4 October 2006 Accepted: 9 October 2006 Published online: 17 November 2006

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.
Keywords Advanced breast cancer - Phase I clinical trial - BZL101 - Scutellaria barbata - Botanical medicine - Complementary and alternative medicine

This clinical trial was supported by the California Breast Cancer Research Program IDEA Award CA-BCRP 7WB-0055. We thank Dr. Laura Esserman for encouraging rigorous scientific research in the area of botanical medicine at the University of California, San Francisco Carol Franc Buck Breast Care Center.