WEDNESDAY, JANUARY 13, 1999
"Analyzing the Traditional Chinese Model of Care for Breast Cancer"

Isaac Cohen, an experienced practitioner of Traditional Chinese Medicine (TCM), joined Dr. Tripathy for tonight's forum on alternative medicine. He has a large practice including many women with breast cancer, and in fact was the leading force in initiating the program at UCSF, including the new clinical trial and some research initiatives. TCM has a very rich and long history, and interest in the West continues to be strong. Large surveys done on alternative medicine within California and throughout the U.S. have shown that between 25 and 30% of women with early stage breast cancer and at least 70% of women with advanced breast cancer will have tried or been interested in it.

The challenge for us is to set up a program that takes into account the realities of chinese and herbal therapy. Therapies are highly individualized; they do not fit easily into a clinical trials methodology. Over time, we hope to be able to integrate it into other therapies used for breast cancer. Initially it was decided to look at herbs which alleviate the side effects of chemotherapy in early stage breast cancer. Isaac's challenge was to put together what this regimen might be. This is challenging because TCM treats the total individual, not just the effects of one illness. To come up with a regimen that only treats the effects of chemotherapy is quite difficult. Next challenge is the design of the trial. After an extensive literature search and Isaac's extensive experience, a particular formula of herbs was chosen that met the criteria of combatting nausea. The formula was then submitted to the FDA along with the trial design. At first a small pilot that looked at safety was planned. It was felt that you could not draw any conclusions about the effect of the therapy with this uncontrolled approach. So a randomized study was planned in which we would take 60 patients who were receiving adriamycin and cytoxan (AC) and randomly assign half to receive the active herb and half to receive the placebo (cornstarch, beets and chicory). Patients assigned to the "active herb" would start to take the placebo/herb for exactly two weeks before therapy (run-in period) to allow the researchers to look for side effects which were due exclusively to the herbal therapy. All patients would then continue onto their assign arm and receive their chemotherapy with only the investigational pharmacist knowing who was assigned to what arm. With chemo, all patients would receive the standard of care anti-nausea medicine. Along with blood work and immunologic studies, a careful symptom inventory will be maintained. At the end of the chemotherapy, patients will continue to take herbs for a total of 180 days. Quality of life measures will be analyzed. The total of 60 patients will allow us to make some preliminary observations about the efficacy of the herbal treatment. The goal of the project is to observe any differences between the herbal group and placebo in alleviating symptoms of chemotherapy such as nausea, hair loss, loss of appetite, mucositis, as well as to see if there is a reduction in the amount of standard nausea medication needed. We will also look at quality of life and safety (liver functions), and save blood to analyze immunologic indices. The protocol has just started, and we are in the process of enrolling our second patient. Anyone who wants further information on this trial should contact the study coordinator Erika Leemann at (415) 885-7328, or e-mail her at Ericka_Leemann@quickmail.ucsf.edu.

We already have found that many people who might be eligible for the study have a strong preference for the herbs and do not want to be randomized for fear that they will be in the control group which only receives the placebo. It is not possible for them to take herbs on one's own during the course of the trial. Another barrier is the two week run in period for those patients who are very anxious to begin their chemotherapy.

Isaac Cohen: In Chinese medicine the main emphasis is on understanding subjective symptoms and putting them in a context that allows you to project what kind of therapy you want to use. This history that is taken is one that includes a very broad history that attempts to explain why things are as they are. The whole system relies heavily on this individual assessment. Trying to design a single formula for a single process like chemotherapy, you must understand the basis of the disease process and how the drugs are going to influence the body and why the side effects occur. It is not enough to alleviate nausea, one must know why the nausea occurs. Then you must project this thought process to the individual. In TCM, it is thought that dietary patterns, menses, lactation, emotional and environmental factors may influence the origination of cancer. In TCM there are approximately 15 herbs that alleviate nausea, but there are 10-12 types of nausea that one encounters. Each one would use a different regimen of herbs. It is believed that if you restore your health quickly enough, the likelihood of recurrence is reduced. The way the herbs are combined can contribute to this.

Dr. Tripathy: The paradox of western medicine is that cancer has been found to be a diverse collection of diseases, there is much heterogeneity on a molecular level, yet there is a singular treatment approach. We use the same drugs for all these different cancers. The oriental approach is highly individualized when done by a highly trained individual. Western medicine needs to begin to follow this approach and tailor therapy to the individual. We are starting to do this when we use hormone therapy with ER+ tumors. There are clearly roles for both powerful western medicine and for natural botanical compounds, what we need is a synthesis of these approaches which can then be applied to individualized care. Integrated medicine will need to use both objective as well as subjective medicine to succeed. Clinical trials are not the optimum way to practice traditional chinese medicine, so there are some limitations, but joint practice is the goal for this model.

Questions:

Q: My understanding of holistic health is that the practitioner wants to re-establish all systems working harmoniously together, including hormones like estrogen. Yet in western thinking, after breast cancer, I should deprive myself of estrogen. How do you reconcile these concepts?
A: There are many flaws in the Chinese system in which they may give hormones to eliminate symptoms which then contribute to the disease process rather than to health. Few Chinese doctors have the training to understand these issues on such a specialized level as in breast cancer. One might try to model something that has a high level of safety taking both schools of thought into account. Maybe use soy products rather than hormone estrogen.

Q: If you take the herbs, will it counteract the effects of the chemotherapy, possibly making your cancer stronger?
A: The goal of our study is to inhibit the effects of the drugs, but not inhibit the effects of the chemotherapy.So far studies in China have shown that herbs+chemo=better outcome, but the studies are not well done. Long term follow-up will be needed, but this is not the goal of our study. What we postulate as outcomes from laboratory studies rarely turn out that way in the clinic. Example: No one really knows how Herceptin works. Centuries of tradition would indicate that herbal therapies are probably okay. How do you test herbal therapies from a rigorous scientific view point? Must look at Chinese medicine as a "black box" (regardless of what treatments are used: herbs, acupuncture, massage) and look at outcomes on both sides of the box. When TCM is applied, do you get a difference in outcome? In a randomized study with TCM vs. No Therapy if you find big differences, how do you know what part is effective? Some would say the study is useless, but although you can't isolate the "active compound", it is still useful to know that it works.

Q: Because of small sample size, how can you be sure that the patient is getting the right type of herb?
A: We will track diagnoses, take pictures of the tongue, evaluate the pulse, take careful measurements and track how patients do in various areas. If at the end we find a subgroup that has, say, kidney insufficiency, we can try to develop a regimen that is more specific for that. We have been funded for a small pilot study that will take 15 patients with metastatic cancer and are taking no therapy. Isaac will be able to practice herbal therapy and acupuncture on them without restriction, and then look at the outcomes. So research in this area is proceeding on multiple fronts. Dr. Tripathy feels that the first question should be does it work? If we wait for why does it work, we may never get there.

Q: How will the herbs be dispensed?
A: Herbs will be freeze dried, ground up; reconstitute with some warm water when drunk. They will still have the bitter taste, but not the smell. Maybe next time a pill form will be tried, but from clinical experience the pill form is not as effective without the interaction with the saliva, even though it tastes better. The placebo looks the same, smells the same, tastes as bad.

Q: I have achieved good effects with acupuncture, which eliminates the worry about estrogen in herbs. Is this effective?
A: In modern China, herbs and acupuncture are not given together. Each therapy has its supporters. Acupuncture has clinically good effects controlling and managing immediate symptoms and also psychophysiological side effects. Herbal medicine has a more drug-like sustained effect. It is harder to create a long term effect with acupuncture. There is a long history of safety with Chinese herbal medicine. But remember: tamoxifen is estrogenic in uterine cells, even though it has valuable anti-estrogen properties overall.
Isaac Cohen: Originally, most patients came to the herbalist for psychological problems. That has begun to change and people now come for more specific ailments. The multifunctions of the herbs relate more to how they think the body works, not necessarily the chemical relationship. We have added an herb that helps to eliminate insomnia because many women diagnosed with breast cancer suffer from this, but we can't do too much of this type of thing because herbs have other effects.

Q: Is there any attempt to combine your patients officially now?
A: Yes, we are currently trying to get an herbalist/acupuncturist credentialled here at UCSF. No major medical center has ever done this before. There is preliminary approval to do acupuncture, but not yet herbs. This is sure to be a long process, with the goal of having an integrated practice-but this is totally experimental.

Q: What about insurance?
A: Third party payors go by "evidence-based medicine". Currently there is not enough evidence for most insurance companies to cover it. People will need to pay out of pocket. For the trial, there will be no cost to the patient since it is a funded project. This joint venture will be carefully detailed to provide outcome information, not as controlled as a clinical trial however. Another issue is economics. As larger parts of the population use alternative medicine insurance companies may be forced to pay. Currently, 2-1/2 times more money is spent on alternative medicine that on standard medical care.

Q: Is it yet possible to predict which chemotherapeutic agent will be most effective in an individual?
A: Some chemosensitivity assays have been somewhat predictive. They can never be fully predictive, because a patient's cells growing in a test tube are simply not the same as the patient herself. These assay labs should be working to get one large prospective study out, because we do not yet have statistics about their effectiveness.

Q: What is the Chinese medicine approach to the use of tamoxifen?
A: There is no standardized approach. It should be used when necessary as when a woman has breast cancer and is ER+. Then you try to alleviate with Chinese medicine some of the problems that tamoxifen causes (hot flashes, etc.).