Chinese Herbal Therapy (CHT) for Symptom Management

Institution: University of California, San Francisco
Investigator(s): Hope Rugo, M.D. -
Award Cycle: 2000 (Cycle VI) Grant #: 6JB-0118 Award: $200,000
Award Type: IDEAS II
Research Priorities
Detection, Prognosis and Treatment>Innovative Treatment Modalities: search for a cure

Initial Award Abstract (2000)
Early stage breast cancer constitutes the majority of the 176,000 cases diagnosed in the US yearly. An increasing proportion of patients benefit from adjuvant hormonal therapy, chemotherapy, and radiation therapy. Despite advances in supportive care, most women experience debilitating side effects during the course of treatment. Alternative and complementary therapies have become highly popular both for management of symptoms and as cancer therapy even though little data from well controlled trials are available. In the San Francisco Bay Area, our group has found that 72% of women used at least one type of alternative modality and about half of them used two types of non-conventional therapies after breast cancer diagnosis. One of the most popular and well-standardized forms of alternative medicine used among women with breast cancer is traditional Chinese medicine (TCM). We propose an innovative research plan that would constitute the first attempt to assess the toxicity and efficacy of a Chinese herbal therapy (CHT) regimen designed by our team as adjunctive treatment to ameliorate multiple side effects of chemotherapy for early stage breast cancer. This clinical trial and outcomes assessment tools have been piloted at the UCSF Breast Care Center with 9 patients and we now propose to conduct the complete Phase I/II randomized, double blind, placebo controlled clinical trial with 60 study participants. The aims of our study are to assess the safety of CHT and to gather preliminary data on efficacy terms of ameliorating symptoms by comparing the CHT treatment group to a control group. The information on safety and feasibility would be necessary to design a future more definitive randomized Phase III study evaluating the efficacy of CHT to abate the side effects of chemotherapy. An effect size would also be estimated from the pilot trial and utilized to calculate the sample size for the Phase III study. This research project is not only innovative in its clinical question but it is also novel by bringing together the expertise of three TCM practitioners with expert clinical trialists to address the usefulness of alternative medicine to treat breast cancer. Ellis model of multi-disciplinary integrative medical research for breast cancer could be applied to numerous other settings and different treatment modalities.

Final Report (2004)
Combinations of Chinese herbs have been used for more than a thousand years to improve symptoms resulting from a wide variety of diseases, as well as the side effects of treatment, as has been suggested to also possibly modulate and improve immune function. Chemotherapy for early stage breast cancer is known to cause many side effects, including nausea and vomiting, fatigue, and bone marrow suppression. Although there are many agents now available to counter these side effects, each medication has its own side effects and limitations in terms of efficacy. Many patients now turn to herbal combinations without proven efficacy or safety testing, with the goal of reducing side effects of chemotherapy and improving immune function. It is clear that rigorous clinical trials are needed to investigate the true impact of these commonly used uncontrolled products.

The specific aims of the study were to assess toxicity and safety of a commonly used and rationally designed combination of Chinese herbs called CT101 in patients with early stage breast cancer and to make preliminary estimates of how well CT101 might work to reduce the side effects of doxorubicin-based adjuvant chemotherapy for breast cancer.

We performed a randomized phase II trial of CT101 in patients receiving highly emetogenic chemotherapy (chemotherapy causing significant nausea) for early stage breast cancer. The trial included women with early stage breast cancer (stages I-III) undergoing doxorubicin/cyclophosphamide (AC) adjuvant chemotherapy or AC followed by paclitaxel chemotherapy, two commonly prescribed chemotherapeutic regimens to lower the risk of breast cancer recurrence. The primary outcome measure for preliminary efficacy analysis was the reduction of both the severity and duration of nausea and vomiting from chemotherapy. Secondary outcome measures included evaluation of changes in immune function that could be attributed to the effects of CT101. Women enrolled to the study were randomly assigned to receive either CT101 or placebo daily, beginning treatment two weeks prior to chemotherapy and ending treatment four weeks after the last AC chemotherapy for a total of 84 days. Side effects, or adverse events (AEs), associated with the study drug were evaluated by the treating physician using standard National Cancer Institute (NCI) Common Toxicity Criteria, version 2. All AE's were recorded and classified according to organ system, coded by grades of severity (I-IV) as well as their relationship to CT101 or chemotherapy. Immune function was assessed by analyzing the patients' white blood cells sampled at six time points during the trial. Thirty-two patients participated in the study. Patients were enrolled at the University of California, San Francisco Carol Franc Buck Breast Care Center and at the Cancer Research Network in Miami, Florida. One patient was consented and not treated with study medication. Twenty-six of the patients completed the 84 day study. Three patients stopped CT101 due to patient preference. There were no serious or moderate toxicities. The majority of patients took all of the prescribed herb. We used the Functional Living Index for Emesis (FLIE) questionnaire as the primary outcome measurement to assess efficacy of the Chinese Herbal Formula. We did not see any difference in scores between the treated and placebo group. There were no consistent differences in immune function noted.

Although this Chinese herbal formula was relatively well tolerated, randomization was a problem in our population of patients and determination of efficacy was compounded by use of multiple other necessary medications. Future trials will need to be powered to detect subtle differences, and include several institutions to avoid geographic bias towards or against herbal formulations during adjuvant chemotherapy for early stage breast cancer.