Complementary And Alternative Medicine Clinical Trials
For Cancer Treatment

by

Deborah Daly, M.S.

A project made possible by the
Carol Ann Schwartz Cancer Education Fund

I. Clinical Trials: An Introduction

Available Clinical Trials

Although in the past few decades, conventional medical treatment has become increasingly effective against cancer, over the long term about half of all cancer patients either fail to respond to treatment or, after apparently successful initial results, experience a recurrence and ultimately die from metastatic or advanced disease. Researchers working within medical schools and hospitals, at government agencies such as the National Cancer Institute (NCI), in private research facilities, and within the pharmaceutical and biotechnology industries are devoting a great deal of effort to finding better cancer treatments and confirming that they are better than the existing ones.

Most academic medical centers (medical schools and the hospitals and other facilities affiliated with them) and many providers of care to cancer patients participate in clinical cancer research that focuses on assessing the effects of new treatments, or known treatments used in new ways, on people with cancer. Some providers choose not to recruit their patients into clinical research studies, either in general or on a case-by-case basis, on the grounds that a sick person should not be subjected to an untested treatment or because they feel that the standard care they offer is superior. Other providers encourage their patients to participate in research on the grounds that the treatment otherwise available is less than ideal and that the experimental treatment has shown enough promise to justify the risk.

The Research Process

Usually a new treatment is tested first on cancer cells in a laboratory. If it seems to be effective against cancer cells, it is tested in animals-usually small mammals, such as mice and rats. If it appears to have an anti-tumor effect in animals and does not have extremely harmful side effects at doses that are large enough to affect the tumor, then it is a candidate for testing in human subjects.

The testing of an experimental treatment in humans is called a clinical trial. The purpose of a clinical trial is to test the safety and effectiveness of new treatments in a small number of patients. Those treatments that prove safer and more effective than previously used treatments can be made available to all patients. Conventional clinical trials are registered with the U.S. government's Food and Drug Administration (FDA) and/or approved by a human subject protection committee. In addition, a clinical trial should have a defined outcome and patient population, and its results should be peer-reviewed (reviewed by a panel of expert scientists). Some studies are called "clinical trials" but do not meet these criteria.

Phase Studies In the research process, many treatments go through a three-part series of clinical studies, called phases. The patient who is considering entering a study should be aware of the differences between these phases studies and be informed about the phase of the study under consideration.

The purpose of a phase I study is to determine the relationship between the dose or dosing schedule of a treatment and harmful side effects. Animal studies cannot provide accurate information about how much of a treatment a human subject can take safely, although the results of animal studies can suggest some rough limits and may also indicate which, if any, organs in a human subject may be harmed by the treatment. Patients who have tried other treatments without success are candidates for participation in phase I studies. It is not necessary for all patients in such a study to have the same type of cancer, but if the treatment is suspected of being harmful to a particular organ, such as the kidneys, that organ should be healthy at the time patients enter the study.

Phase II studies are carried out to determine which types of cancers are most likely to be affected by the treatment in question. Phase II studies usually involve larger numbers of participants than phase I studies. For comparison, Phase II studies sometimes include control groups of patients with comparable disease histories who receive a standard (widely accepted) treatment rather than the experimental treatment; these studies may also include patients who have not had any other treatment.

The purpose of a phase III study is to determine whether a new treatment is more effective, or associated with less severe side effects, than a standard treatment for a particular type of cancer. Phase III studies always include a control group and usually include more participants than phase II studies. From a scientific standpoint, in the ideal study, participants with a single type of cancer are randomly assigned to receive either an experimental treatment or a standard, control-group treatment neither the participants nor the physicians or other caregivers who are assessing the results of treatment know which treatment any one participant is receiving. Concealing treatment assignment in this way is called double-blinding.

Defined Endpoints An important aspect of phase II and III clinical trials is the endpoint, or outcome-the designated point at which a study concludes and a particular treatment is declared a success or failure. The endpoint is based on the type and severity of disease under study and the desired effect of the treatment. The endpoint that is of greatest interest to most cancer patients is cure-being permanently free of cancer. However, many treatments cause a cancer to disappear only in the short term. Duration of survival or duration of survival without cancer recurrence (disease-free survival) is also used as an endpoint. These studies may be based on five or more years of follow-up.

For some patients with certain types of cancer, treatment appears to be successful for a number of years, but then the cancer reappears. Recurrent cancer is typically much harder to treat than newly diagnosed cancer that has never been treated before. Patients who have experienced a recurrence are often at increased risk for another recurrence. They may fall into a pattern of further treatment followed by further recurrence, often accompanied by treatment side effects and increasing debilitation, followed by metastasis (spread of cancer) and death. For these patients, the endpoints of interest may include tumor regression, either partial or complete; reduction in symptoms (such as fatigue or pain) or side effects (such as nausea or mouth sores); or improvement in function (such as ability to climb stairs) or mood.

Research in Alternative and Complementary Medicine

The field of alternative and complementary medicine has been characterized by practice-based research-that is, research based on contacts with patients during the ordinary course of treatment. Essentially, most doctors interested in alternative and complementary medicine who are working in the cancer field are doctors first and researchers second. The simplest form of such research, and the most common in the field of alternative and complementary medicine, is the case history, or "anecdotal report." Although many researchers abstain from such studies because they are not considered "scientifically rigorous," the case history is a time honored way of reporting unusual outcomes. Distinguished medical journals, such as the New England Journal of Medicine, routinely publish them. A report of a particular treatment in a group of patients may be called a "case series" or a "single group trial."

As more money becomes available for research on alternative and complementary medicine, more sophisticated research approaches are emerging. However, such features as the individualization of treatment are incompatible with the standards usually required for conventional clinical trials. Conducting research on alternative and complementary medicine that is accepted as valid by both conventional and unconventional medical communities will require special planning, resources, and creativity.

Locating Clinical Trials

The National Cancer Institute (NCI) supports a number of clinical trials and maintains a database of these, which physicians can access on behalf of their patients. Patients who wish to participate in such trials can ask their physicians whether they are eligible. The database is accessible both via an 800 telephone number (1-800-4-CANCER) and on the Internet ( http://wwwicic.nci.nih.gov/patient.htm). In addition, a number of clinical trials under other sponsorship are in progress.

An annotated list of clinical trials in complementary and alternative medicine follows. Keep in mind that this list does not represent the full extent of available complementary and alternative modalities.

II. Available Clinical Trials of Complementary and Alternative Treatments for Various Cancers

Dr. Burzynski's Clinical Trials with Antineoplastons for Many Types of Cancer

At the behest of the FDA, Dr. Stanislaw Burzynski has established clinical trials for virtually all his patients. These trials involve the oral or intravenous administration of antineoplastons, a group of peptides (protein fragments) that are normally synthesized by the body in low concentrations. Prospective patients are reported to the FDA, which decides whether or not admission is warranted in each case. Thus, the patient should be aware that Dr. Burzynski does not decide on his own when to accept a patient for treatment. In addition, treatment with Dr. Burzynski's antineoplastons in these clinical trials can be expensive. It is unclear who evaluates the cases once the clinical trials have been completed.

Contact: Stanislaw R. Burzynski, M.D., Ph.D.

Internal Medicine

12000 Richmond Ave., Suite 260

Houston, TX 77082-2431

(713) 597-0111

Inclusion criteria:

The inclusion criteria differs for each study depending on the health history of the patient and the type and stage of the cancer.

Exclusion criteria: none specified.

Cancers being studied:

Adrenal Gland Cancer

Bladder Cancer

Brain Cancer- high grade glioma (in children); glioblastoma multiforme; anaplastic astrocytoma; brain stem glioma (in children); low grade astrocytoma (in children and adults); rhaboid tumor of the central nervous system (in children); oligodendroglioma; mixed glioma; neurofibroma and schwannoma; primary malignant brain tumors (in children and adults); visual pathway glioma (in children); ependyoma; craniopharyngioma; choroid plexus neoplasm; germ cell tumor of the brain; meningioma.

Breast Cancer

Female Reproductive Tract Cancers- carcinoma of the ovary; carcinoma of the uterus, cervix, and/or vulva.

Gastrointestinal Cancers- carcinoma of the small intestine; adenocarcinoma of the rectosigmoid; adenocarcinoma of the stomach; adenocarcinoma of the esophagus; adenocarcinoma of the colon.

Head and Neck Cancers

Kidney Cancer- renal cell carcinoma.

Leukemia - chronic myelogenous leukemia.

Liver Cancer- hepatoblastoma (in children).

Lung Cancer- adenocarcinoma of the lung; large cell undifferentiated carcinoma of the lung; bronchial alveolar carcinoma of the lung; squamous cell carcinoma of the lung; small cell carcinoma of the lung.

Lymphoma- low, intermediate and high grade non-Hodgkins lymphoma; mantle zone lymphoma; primary central nervous system lymphoma; primary lymphoma of the gastrointestinal tract.

Melanoma- multiple melanoma; malignant melanoma.

Pancreatic Cancer

Prostate Cancer- adenocarcinoma of the prostate.

Skin Cancers- mycosis fungoides.

Miscellaneous Cancers: refractory malignancies; soft tissue sarcoma, neurendocrine tumors, primitive neuroectodermal tumors, Wilms tumor, carcinoma of unknown primary origin.

Dr. Burzynski's clinic is also conducting a randomized control trial comparing methotrexate treatment alone to the combination of methotrexate and antineoplaston A10.

Dr. Gonzalez's Clinical Trials of an Intensive Nutritional Program for Pancreatic Cancer

Patients are closely monitored for two years on this nutritional program which involves diet, nutritional supplementation, and detoxification. Dr. Nicholas Gonzalez's clinical trials follow a more standard format than those of Dr. Burzynski (see above). The trial has a delineated population with clearly stated goals and exclusion criteria. There is an outside review board of six experts who oversee the conduct and outcome of the treatment. The National Cancer Institute is involved in an informal way in monitoring the trial. In addition, like most conventional clinical trials, the cost of the treatment is free to the patients who are accepted. In this case, these costs are being met by a grant from the research department of Proctor and Gamble.

At the present time, the Gonzalez clinical trial has reached its limit of ten patients with pancreatic cancer. Clinical trials for those with metastatic lung or metastatic colon cancer have also been proposed, but these have not yet started. Strict criteria must be met in order to be included in Dr. Gonzalez's trials. Previous exposure to chemotherapy and/or radiation can be grounds for exclusion.

Contact:

Nicholas J. Gonzalez, M.D.

36 East 36th Street, Suite 204

New York, N.Y. 10016

(212) 213-3337

Inclusion criteria:

Patients must have biopsy proven disease diagnosed within two months of entering the study.

Exclusion criteria:

Chemotherapy, radiation, and certain surgical procedures like the whipple procedure are grounds for exclusion.

Cancers being studied:

Pancreatic Cancer

Admission is CLOSED for the pancreatic cancer trial, but several new studies will be started in the near future.

Dr. Simone's Clinical Trials of Shark Cartilage and Lifestyle Modification for Lung, Breast, Colorectal, Prostate, Bladder, Brain, and Lymphoma Tumors

Dr. Charles Simone's trial for seven types of cancer is an FDA-registered protocol. Dr. Simone is investigating the use of shark cartilage and lifestyle modification for the treatment of patients with advanced cancers. The protocol involves the oral ingestion of 80 grams (7 teaspoons) of shark cartilage three times a day for 16 weeks. Each patient is also instructed on the Simone Ten Point Lifestyle Plan. This clinical trial is not funded by an outside agency. Except for Medicare patients, the cost of Dr. Simone's office visits are the responsibility of the patient. In addition to the FDA, an outside panel of physicians will review the results of the study.

Contact: Charles B. Simone, M.D.

Simone Protective Cancer Institute

123 Franklin Corner Road

Lawrenceville, N.J. 08648

(609) 896-2646

Inclusion criteria:

Incurable, advanced cancer with progressive disease and a life expectancy of at least 12 weeks; prior treatment with chemotherapy, radiation, and/or surgery (except for those with renal cancer and melanoma, and not if treatment was administered within the preceding six weeks); a histologic diagnosis; objective measurable disease of at least 1 x 1 cm in size; at least 18 years of age; adequate kidney, marrow, and liver function; and no prior cartilage use during previous therapies.

Exclusion criteria:

Radiation therapy to brain for primary tumor within 45 days prior to enrollment; use of cartlage concomitant with other therapy; chemotherapy, radiation or major surgery within 3 weeks preceding study entry; chemotherapy with nitroso-ureas or mitomycin within 6 weeks preceding study entry; pregnant or lactating women

Cancers being studied:

Bladder Cancer

Brain Cancer

Breast Cancer

Colorectal Cancer

Lymphoma

Lung Cancer

Prostate Cancer

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