Table of Contents

Overview
General Information
History
Laboratory/Animal/Preclinical Studies
Human/Clinical Studies
Adverse Effects
Levels Of Evidence
Glossary Of Terms
References
For More Information

Overview

This complementary and alternative medicine (CAM) information summary provides an overview of the use of 714-X as a treatment for cancer. The summary includes a brief history of 714-X research; a review of laboratory, animal, and human studies; and possible side effects of 714-X use. A glossary of scientific terms used in the summary appears just before the references. Terms defined in the glossary are marked in the text by hypertext links.

General Information

714-X was developed over 30 years ago in a privately funded laboratory in Quebec, Canada, where it continues to be produced. The primary component of 714-X is naturally-derived camphor that has been chemically altered by the addition of an extra nitrogen atom and then combined with ammonium salts, sodium chloride, and ethanol.[reviewed in 1]

The laboratory currently makes 714-X available through physicians in Canada (where it is available on compassionate grounds only, but not approved for general therapeutic use), Mexico, and some western European countries.[reviewed in 1] Since the production of 714-X is not regulated, there is no guarantee that rigorous quality control procedures are followed to assure manufacturing consistency and product safety. The Food and Drug Administration (FDA) has not approved 714-X for use in the United States.

Before researchers can conduct clinical drug research in the United States, they must file an Investigational New Drug (IND) application with the FDA. The IND application process is highly confidential, and IND information can only be disclosed by the applicants. To date, no investigators have announced that they have applied for an IND to study 714-X as a treatment for cancer.

714-X is usually administered by injection into lymph nodes in the groin, but it can be administered nasally, using a nebulizer, for patients with lung or oral cancers. The producers of 714-X do not recommend intravenous or oral administration. A usual treatment cycle consists of daily injection for 21 days followed by a 3-day rest period. Between three and 12 treatment cycles are recommended, depending on the stage of the cancer. It has been suggested that 714-X is more effective if administered early in the disease process and before chemotherapy or radiation therapy, but that it can also be used in conjunction with conventional treatments. It has been recommended that vitamin B12 supplements, vitamin E supplements, and alcohol be avoided during 714-X therapy.[reviewed in 1]

History

Little documentation exists regarding the development of 714-X and its mechanism of action. It appears to have been developed in the 1960s on the basis of earlier studies that used a high-magnification, dark-field microscope, called a somatoscope.[reviewed in 1,2] With the somatoscope, researchers were able to examine living cells in fresh blood and tissue samples taken from healthy individuals and individuals with serious diseases, including cancer. The study of living cells (as opposed to the dead cells examined with a conventional light microscope or an electron microscope) led to the theory that microorganisms distinct from bacteria, viruses, and fungi exist normally in the blood and play a role in cancer development. These microorganisms, which were called"somatids," are said to exist in multiple forms, some of which appear only in individuals with degenerative diseases or cancer. The forms associated with disease reportedly secrete toxic substances and growth hormones that disrupt normal cellular metabolism and damage the immune system. In this compromised environment, cells that have become cancerous are allowed to proliferate. It was also suggested that cancer cells trap nitrogen, thereby depriving the rest of the body of the nitrogen needed for normal cellular metabolism. In addition, it was proposed that cancer cells secrete a toxic substance (co-cancerogenic K factor) that further inhibits the immune system.[reviewed in 1,2] The producers of 714-X state that cancer can be diagnosed, and its development and spread can be predicted, by studying blood samples with the somatoscope. No evidence has been published in peer-reviewed, scientific journals to support these proposals, and the somatid theory of cancer development is not widely accepted.

It has been proposed that 714-X works by protecting, stabilizing, and reactivating the patient's immune system, so the body can defend itself against tumor growth and metastasis. The camphor component of 714-X is purportedly attracted to cancer cells, where the added nitrogen is released, thus preventing tumor cells from depleting the nitrogen required by normal cells, including immune system cells, for proper metabolism and function.[reviewed in 1,2]

Laboratory/Animal/Preclinical Studies

There have been no laboratory or animal studies published in peer-reviewed, scientific journals in which the safety or the efficacy of 714-X was evaluated. Results of studies using tumor models in rats, dogs, and cows were presented at a scientific conference in 1982, and no benefit of 714-X could be demonstrated.[reviewed in 1]

A few laboratory and animal studies have suggested that camphor (a component of 714-X) may be able to enhance the immune response observed after vaccine administration and increase the sensitivity of tumor cells to radiation therapy.[3-7] In one series of studies, investigators used camphor vapors as a "conditioned stimulus" to promote an immune response.[3-6] These studies demonstrated that mice exposed to camphor vapors at the same time they received an antitumor vaccine showed decreased growth of transplanted lymphoma cells and increased survival when they were re-exposed to camphor vapors plus the vaccine or to camphor vapors alone, in comparison with mice re-exposed to only the vaccine.[3,4] These investigators also demonstrated that exposure to camphor vapors led to an increase in natural killer cells [5] and in tumor-specific cytotoxic T cells.[6] Another study reported that breast adenocarcinoma cells transplanted under the skin of mice responded better to local radiation therapy when small doses of camphor were given by intraperitoneal injection before irradiation.[7] Finally, researchers examined nine compounds, including a camphor-containing compound, for their ability to inhibit the activity of estrone sulfatase, an enzyme involved in the production of estrone, which is a precursor of the various forms of estrogen. Estrogens are thought to promote the growth of hormone-dependent breast cancer cells. The camphor-containing compound showed only modest inhibition of estrone sulfatase activity in human breast cancer cells grown in the laboratory.[8]

Human/Clinical Studies

No clinical trials, clinical series, or case reports have been published in peer-reviewed, scientific journals to support the efficacy or safety of 714-X. A number of anecdotal reports and testimonials have been published in newspapers and other non-medical literature. The producers of 714-X state that they have tried to document the long-term experience of patients treated with 714-X, but they have encountered difficulty in obtaining information from patients and their health-care providers.[reviewed in 1]

Adverse Effects

714-X is reported to be nontoxic, with the only side effects of treatment being local redness, tenderness, and swelling at injection sites.

Levels of Evidence for Human Studies of Cancer Complementary and Alternative Medicine

To assist readers in evaluating the results of human studies of CAM treatments for cancer, the strength of the evidence (i.e., the "levels of evidence") associated with each type of treatment is provided whenever possible. To qualify for a levels of evidence analysis, a study must 1) be published in a peer-reviewed, scientific journal; 2) report on a therapeutic outcome(s), such as tumor response, improvement in survival, or measured improvement in quality of life; and 3) describe clinical findings in sufficient detail that a meaningful evaluation can be made. No levels of evidence analysis could be performed for 714-X because no study of its use in humans has been published in a peer-reviewed, scientific journal. For additional information about levels of evidence analysis of CAM treatments for cancer, please click on the following link: Levels of Evidence Analysis for Human Studies of Cancer Complementary and Alternative Medicine.

Glossary of Terms

adenocarcinoma: Cancer that begins in cells that line certain internal organs and that have glandular (secretory) properties.

anecdotal report: An incomplete description of the medical and treatment history of one or more patients. Anecdotal reports may be published in places other than peer- reviewed, scientific journals.

camphor: A substance that comes from the wood and bark of the camphor tree or is made in the laboratory. It has a very unique smell and taste and is used in commercial products (for example, mothballs). Camphor is used in topical anti-infective and anti-pruritic (anti-itching) agents.

case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin).

chemotherapy: Treatment with anticancer drugs.

clinical series: A case series in which the patients receive treatment in a clinic or other medical facility.

clinical trial: A research study that evaluates the effectiveness of new interventions in people. Each study is designed to evaluate new methods of screening, prevention, diagnosis, or treatment of a disease.

complementary and alternative medicine: CAM. Forms of treatment in addition to (complementary) or instead of (alternative) standard treatments. These practices include dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation.

conditioned stimulus: A situation in which one signal, or stimulus, is given just before another signal. After this happens several times, the first signal alone can cause the response that would usually need the second signal.

cytotoxic: Cell-killing.

cytotoxic T cells: A type of white blood cell that can directly destroy specific cells. T cells can be separated from other blood cells and grown in the laboratory and then given to the person to destroy tumor cells. Certain cytokines can also be given to people to assist in the formation of cytotoxic T cells within the person's body.

dark-field microscope: A microscope (device used to magnify small objects) in which objects are lit at a very low angle from the side so that the background appears dark and the objects show up against this dark background.

derivative: In chemistry, a compound produced from or related to another.

electron microscope: A microscope (device used to magnify small objects) that uses electrons (instead of light) to produce an enlarged image. An electron microscope shows tiny details better than any other type of microscope.

enzyme: A protein that speeds up the rate at which chemical reactions take place in the body.

intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs).

intravenous: IV. Into a vein.

light microscope: A microscope (device used to magnify small objects) in which objects are lit directly by white light.

lipids: Fats.

lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and they contain many lymphocytes, which filter the lymphatic fluid (lymph).

lymphoma: Cancer that arises in cells of the lymphatic system.

lysosome: A sac-like compartment inside a cell that has enzymes that can break down cellular components that need to be destroyed.

metabolism: The total of all chemical changes that take place in a cell or an organism. These changes produce energy and basic materials that are needed for important life processes.

metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors," and contain cells that are like those in the original (primary) tumor. The plural is metastases.

microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms.

natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL).

nasal: By or having to do with the nose.

nebulizer: A device used to turn liquid into a fine spray.

oral: By or having to do with the mouth.

quality of life : The overall enjoyment of life. Many clinical trials measure aspects of a person's sense of well-being and ability to perform various tasks in order to assess the effects that cancer and its treatment have on the person.

radiation therapy: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials (radioisotopes) that produce radiation that are placed in or near a tumor or in the area where cancer cells are found (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy involves giving a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy.

stage: The extent of a cancer within the body, including whether the disease has spread from the original site to other parts of the body. Staging refers to the determination of the extent of cancer.

T cell: One type of white blood cell that attacks virus-infected cells, foreign cells, and cancer cells. They also produce a number of substances that regulate the immune response.

testimonials: Information provided by individuals who claim to have been helped or cured by a particular product. The information provided lacks the necessary elements to be evaluated in a rigorous and scientific manner and is not used in the scientific literature.

therapeutic: Used to treat disease and help healing take place.

tumor model: A type of animal model which can be used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models.

vaccine: A compound or group of compounds designed to produce an immune response to a tumor or to microorganisms, such as bacteria or viruses.

References:

1. Kaegi E, on behalf of the Task Force on Alternative Therapies of the Canadian Breast Cancer Research Initiative: Unconventional therapies for cancer, 6: 714-X. Canadian Medical Association Journal 158(12): 1621-1624, 1998.

2. Hess DJ: Can Bacteria Cause Cancer?: Alternative Medicine Confronts Big Science. New York, NY: New York University Press, 1997: pp. 45-47.

3. Hiramoto RN, Hiramoto NS, Rish ME, et al.: Role of immune cells in the Pavlovian conditioning of specific resistance to cancer. International Journal of Neuroscience 59(1-3): 101-117, 1991.

4. Ghanta VK, Hiramoto NS, Solvason HB, et al.: Conditioning: a new approach to immunotherapy. Cancer Research 50(14): 4295-4299, 1990.

5. Ghanta VK, Hiramoto NS, Solvason HB, et al.: Conditioned enhancement of natural killer cell activity, but not interferon, with camphor or saccharin-LiCl conditioned stimulus. Journal of Neuroscience Research 18(1): 10-15, 1987.

6. Ghanta VK, Hiramoto NS, Soong SJ, et al.: Conditioning of the secondary cytotoxic T-lymphocyte response to YC8 tumor. Pharmacology, Biochemistry, and Behavior 50(3): 399-403, 1995.

7. Goel HC, Roa AR: Radiosensitizing effect of camphor on transplantable mammary adenocarcinoma in mice. Cancer Letters 43(1-2): 21-27, 1988.

8. Howarth NM, Purohit A, Reed MJ, et al.: Estrone sulfonates as inhibitors of estrone sulfatase. Steroids 62(4): 346-350, 1997.