Herba Scutellaria Barbatae for Metastatic Breast Cancer

Institution: University of California, San Francisco
Investigator(s): Hope Rugo, M.D. -
Award Cycle: 2001 (Cycle VII) Grant #: 7WB-0055 Award: $232,364
Award Type: STEP Award
Research Priorities
Detection, Prognosis and Treatment>Innovative Treatment Modalities: search for a cure

Initial Award Abstract (2001)
Many patients with metastatic breast cancer use Chinese herbal therapy, despite the fact that its effectiveness has yet to be scientifically documented. We have recently shown that an extract of Herba Scutellaria Barbatae (HSB), a Chinese herb traditionally used to treat MBC, inhibits the growth of breast cancer cells in the laboratory. We believe that HSB presents an ideal model for studying Chinese herbal therapy in controlled clinical trials and have obtained permission from the FDA to administer it to women with metastatic breast cancer. The UCSF review board through a process that involves breast cancer advocates has approved our study design. We will also conduct animal studies to determine how HSB is metabolized and distributed within the body.

We hypothesize that HSB can be safely given to women with metastatic breast cancer and studied by controlled clinical trials in the same scientific manner as other Western-style drugs. The HSB trial has been designed to gather safety data, as well as preliminary measures of tumor growth. Subjects will be 25 patients with metastatic breast cancer, who will drink a tea containing HSB as their only cancer therapy for 1 year or until there is progression of cancer. Patients’ cancer will be evaluated at the beginning of the study and thereafter at 3-month intervals by both physical examination and X-ray scans; side effects will be monitored monthly. Standard statistical measures will be used to analyze the data in regards to safety, toxicity, anti-tumor activity and quality of life. Laboratory techniques will be used to evaluate how HSB is stored and distributed in the body. Breast cancer advocates are involved in the review and design of all breast cancer-related clinical trials at UCSF and also have developed an education and outreach plan for clinical trial participation at UCSF. Much support has been shown in this general area of study.

This study presents an innovative design for studying alternative therapies for breast cancer, such as Chinese herbal therapy, using scientifically rigorous clinical trials. It will provide women who use Chinese herbal therapy accurate information about the safety and effectiveness of this particular herbal compound. Our work can serve as a model to other investigators interested in studying alternative therapies in a scientifically-controlled environment. However, the ultimate benefit will be for patients, who will be able to make the same informed decisions about alternative therapies as they can about conventional pharmaceutical agents. This study can serve as a model for future trials that may identify other herbal agents that could be beneficial in treating advanced breast cancer.

Final Report (2005)
Metastatic breast cancer remains an incurable disease despite advances in early detection and adjuvant therapy. Commonly used hormonal and chemotherapeutic agents lead to transient regression of tumors and palliate symptoms related to cancer. However, these treatments are often accompanied by toxicities and intolerable side effects and eventually become ineffective in controlling advanced stage breast cancer and its symptoms. Improvements in survival are modest even with newer targeted biological agents. Novel therapies with minimal toxicities are clearly needed for this patient population.

It is interesting to note that greater than 60% of all chemotherapeutic agents used in the treatment of breast cancer are derived from natural substances. Throughout the world, it is estimated that approximately 80% of the world population still rely on botanical medicine as their primary source of therapy. In the West, botanical medicine is considered a popular form of complementary and alternative medicine among patients diagnosed with cancer. Few clinical trials have been conducted to firmly assess the safety and efficacy of botanical agents for the treatment of breast cancer despite anecdotal case reports of cures and clinical efficacy in women who have relied solely on botanical medicine for treatment. Scutellaria Barbata (skullcap) is a commonly used herb in Chinese medicine for the treatment of inflammatory conditions and cancer. We have previously shown that a liquid form of this herb can decrease growth of breast cancer cells in cultures. This herb was found to be able to kill cancer cells in animal models as well

We performed a phase I, dose escalated trial of BZL101 in patients with histologically confirmed metastatic breast cancer and measurable disease. Patients could not receive any other chemotherapy, hormone therapy or herbal medicine. Patients initially received 350 ml (12 grams dry solubles) per day of extract in tea form until disease progression, toxicity or personal preference to discontinue. The primary endpoints were safety, toxicity and tumor response.

Twenty-one patients were enrolled, signed informed consent, and received BZL101. Mean age was 54 years (30 - 77) and mean number of prior treatments for metastatic breast cancer was 3.9 (0-10). The primary toxicities of treatment were low level nausea, diarrhea, headache, vomiting, constipation and fatigue. Patients universally complained of a bitter and unpalatable taste. Sixteen patients were evaluable for response. Four of the 16 patients had stable disease (SD) for >90 days (25%) and 3/16 had SD for >180 days (19%). Five patients had minor objective tumor regression, one of which was 1 mm short of a partial remission (PR) based on standard criteria (RECIST).

BZL 101 is safe and has a favorable tolerability profile at the tested dose. The major toxicities were gastrointestinal, but at a low level. BZL101 demonstrates encouraging clinical activity in this heavily pretreated population. BZL has been reformulated as a more palatable tea, and a larger phase I/II trial is planned in patients with minimally treated advanced breast cancer. Traditional herbal extracts can be formally tested using standard clinical trial methods. This has important implications for the study of herbal extracts that may have significant anti-tumor effects, and therefore, clinical impact.

Symposium Abstract (2003)
Herba Scutellaria Barbatae or BZL 101 is a plant derived antiproliferative agent that induces programmed cell death (apoptosis) in variety of breast cancer cell lines in the laboratory (MCF7, BT474, MDA231MB, SKBR and the murine line MCNeu). BZL101 inhibits the growth of doxorubicin (adriamycin) resistant cells, MCF7-ADR, as well as a variety of other cancer cells including lung, pancreatic and prostate (A549, LLC, Panc1, Panc2, PC3). Treatment of transgenic mice with xenograft tumor by IP injection of BZL101 inhibits tumor growth. We designed a phase I/II clinical trial to assess toxicity and preliminary efficacy of this traditional Chinese herbal extract when used to treat metastatic breast cancer (MBC). A total of 25 patients with a histologically confirmed diagnosis of breast cancer will be enrolled in this trial. Eligibility for this trial includes clinical evidence of measurable MBC, minimal symptoms related to cancer, no immediate risk of organ or tissue damage as a result of short-term tumor progression, and no other antitumor treatment including hormone and chemotherapy, and investigational or herbal/alternative agents other than BZL 101. A total of 25 patients were to be enrolled on dose escalated BZL, administered as a tea given with juice twice daily. Toxicity is monitored at each visit. Patients are enrolled at UCSF and at the Cancer Research Network in Florida.

Results: To date 14 of 25 patients have been enrolled. The first 11 patients on study received the starting dose of 200mls twice a day; the last 3 patients received the first escalated dose of 400mls twice a day. Of the 14 patients, 3 patients discontinued treatment due to relatively minor (grade 1) toxicity at 5, 16 and 35 days on study. One patient chose to stop therapy after 169 days to pursue standard treatment. At the time study drug was discontinued, there was slight evidence of disease progression. Ten of the 14 patients had progressive disease. The average time to disease progression was 105 days on study, ± 97.2 SD, with a range of 33–271 days, to disease progression. Two patients at the first dose escalation had intolerable gastrointestinal side effects (grade 2 maximum). The study has since been amended to continue at the starting dose without dose escalation. The most common complaints were mild diarrhea, nausea and fatigue that rarely required therapeutic intervention. No major or life-threatening (hematologic or visceral grade III or IV) toxicities are observed. Two of the patients had minor disease regression (25% and 28% in largest diameter) that did not meet standard partial regression criteria. Of the fourteen patients, the average time on trial is 91.6 days ± 91.73 SD, (with a range of 271–5 days). Three of the patients had more than 260 days on trial. Accrual to this trial is ongoing; updated data will be presented.