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Back To Vidyya Management And Therapy Of Sickle Cell Disease

Complementary/Alternative Medicine

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 is an overview of the use of laetrile as an anticancer treatment. The summary includes a history of laetrile research, a review of laboratory studies, the results of clinical trials, and possible side effects of laetrile 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

The term "laetrile" is an acronym (laevorotatory and mandelonitrile) used to describe a purified form of the chemical amygdalin, a cyanogenic glucoside (a plant compound that contains sugar and produces cyanide) found in the pits of many fruits and raw nuts and in other plants, such as lima beans, clover, and sorghum.[reviewed in 1-5] In the 1970s, laetrile gained popularity as an anticancer agent. By 1978, more than 70,000 individuals in the United States were reported to have been treated with it.[reviewed in 2,6,7] Laetrile has been used for cancer treatment both as a single agent and in combination with a metabolic therapy program that consists of a specialized diet, high-dose vitamin supplements, and pancreatic enzymes.[8, reviewed in 9]

In the United States, researchers must file an Investigational New Drug (IND) application with the Food and Drug Administration (FDA) to conduct clinical drug research in human subjects. In 1970, an application for an IND to study laetrile was filed by the McNaughton Foundation (San Ysidro, California). This request was initially approved, but later rejected because preclinical evidence in animals showed that laetrile was not likely to be effective as an anticancer agent [reviewed in 3,10,11] and because there were questions about how the proposed study was to be conducted.[reviewed in 12] Laetrile supporters viewed this reversal as an attempt by the U.S. government to block access to new and promising cancer therapies, and pressure mounted to make laetrile available to the public. Court cases in Oklahoma, Massachusetts, New Jersey, and California challenged the FDA's role in determining which drugs should be available to cancer patients. Consequently, laetrile was legalized in more than 20 states during the 1970s. In 1980, the U.S. Supreme Court overturned decisions by the lower courts, thereby re-affirming the FDA's position that drugs must be proven to be both safe and effective before widespread public use.[reviewed in 2,13] As a result, the use of laetrile as a cancer therapy is not approved in the United States, but it continues to be manufactured and administered as an anticancer treatment, primarily in Mexico.

Although the names laetrile, LaetrileŽ, and amygdalin are often used interchangeably, they are not the same product. The chemical composition of U.S. patented LaetrileŽ (mandelonitrile-beta-glucuronide), a semi-synthetic derivative of amygdalin, is different from the laetrile/amygdalin produced in Mexico (mandelonitrile beta-D-gentiobioside), which is made from crushed apricot pits.[reviewed in 14,15] Mandelonitrile, which contains cyanide, is a structural component of both products.[reviewed in 14] It has been proposed that cyanide is the active cancer-killing ingredient in laetrile, but two other breakdown products of amygdalin, prunasin (which is similar in structure to LaetrileŽ) and benzaldehyde, may also be cancer cell inhibitors.[16,17,18,19] The studies discussed in this summary used either Mexican laetrile/amygdalin or the patented form. In most instances, the generic term "laetrile" will be used here; however, a distinction will be made between the products when necessary.

Laetrile can be administered orally as a pill, or it can be given by injection (intravenous or intramuscular). It is commonly given intravenously over a period of time followed by oral maintenance therapy. The incidence of cyanide poisoning is much higher when laetrile is taken orally [20, reviewed in 21,22] because intestinal bacteria and some commonly eaten plants contain enzymes (beta-glucosidases) that activate the release of cyanide after laetrile has been ingested.[reviewed in 16,21] Relatively little breakdown to yield cyanide occurs when laetrile is injected.[reviewed in 6,21] Administration schedules and the length of treatment in animal models and humans vary widely.




History

Amygdalin was first isolated in 1830 by two French chemists.[reviewed in 3,22] It was used as an anticancer agent in Russia as early as 1845, with positive results reported for the first patient treated.[reviewed in 5] Its first recorded use in the United States as a treatment for cancer occurred in the early 1920s.[reviewed in 2] At that time, amygdalin was taken in pill form; however, the formulation was judged too toxic, and the work was abandoned. In the 1950s, a purportedly nontoxic intravenous form of amygdalin was patented as LaetrileŽ.[reviewed in 3,14,15]

Laetrile has been tested on cultured animal cells (cells grown in specialized containers in the laboratory), in whole animals, in xenograft models (tumor cells from one species transplanted onto another species), and in humans to determine whether it has specific anticancer properties (an ability to kill cancer cells more readily than normal cells). As noted previously (General Information section), cyanide is believed to be the active cancer-killing ingredient in laetrile.[16,17] When amygdalin interacts with the enzyme beta-glucosidase, or undergoes hydrolysis (breakdown in a reaction with water) in the absence of enzymes, hydrogen cyanide, benzaldehyde, and glucose (sugar) are produced.[reviewed in 3,9,15,16,23] Cyanide can also be produced from prunasin, which is a less-than-complete breakdown product of amygdalin.[reviewed in 3,16]

Four different theories have been advanced to explain the anticancer activity of laetrile. The first of these incorporates elements of the trophoblastic theory of malignancy, a theory that is not widely accepted as an explanation for cancer formation. According to the trophoblastic theory, all cancers arise from primordial germ cells (cells that, under normal circumstances, give rise to eggs or sperm), some of which become dispersed throughout the body during embryonic development and are not confined to the testes and ovaries. The trophoblastic theory also suggests that transformation of primordial germ cells to a cancerous state is normally prevented by enzymes from the pancreas, and that cancers can be destroyed by pancreatic enzyme supplements and treatment with laetrile.[24, reviewed in 25-29] The rationale for laetrile use is the suggestion that malignant cells have higher than normal levels of an enzyme called beta-glucuronidase (which is different from the aforementioned enzyme beta-glucosidase) and that they are deficient in another enzyme called rhodanese (thiosulfate sulfurtransferase). It has been suggested further that laetrile is modified in the liver and that beta-glucuronidase breaks the modified compound down, ultimately producing cyanide. Rhodanese can convert cyanide into the relatively harmless compound thiocyanate. Thus, it has been proposed that cancer cells are more susceptible to the toxic effects of laetrile than normal cells because of an imbalance in these two enzymes.[reviewed in 9,25,30,31,32] It is important to note that there is no experimental evidence to support the idea that normal tissues and malignant tissues differ substantially in their concentrations of beta-glucuronidase or rhodanese.[33,34]

The second theory states that cancer cells contain more beta-glucosidase activity than normal cells and, as in the first theory, that they are deficient in rhodanese.[reviewed in 2,3,21,25,27,30,35] Evidence from laboratory studies demonstrates that this theory cannot be supported. As noted previously, normal cells and cancer cells contain similar amounts of rhodanese.[33] Furthermore, most types of mammalian cells contain only small traces of beta-glucosidase,[34] and this enzyme has not been detected in tumor samples [16,36] or in human blood.[2] Without sufficient levels of beta-glucosidase, it is difficult for intravenously administered amygdalin to be broken down into cyanide and other products.

The third theory states that cancer is the result of a metabolic disorder caused by a vitamin deficiency. It states further that laetrile, or "vitamin B-17," is the missing vitamin needed by the body to restore health.[reviewed in 6,30,37,38] Experimental evidence indicates that the level of intake of individual vitamins and/or the vitamin status of an organism can influence the development of cancer, but there is no evidence that laetrile is needed for normal metabolism or that it can function as a vitamin in animals or humans.[reviewed in 39,40]

The fourth theory suggests that the cyanide released by laetrile has a toxic effect beyond its interference with oxygen utilization by cells. According to this theory, cyanide increases the acid content of tumors and leads to the destruction of lysosomes (compartments inside cells that contain enzymes capable of breaking down other cellular molecules). The injured lysosomes release their contents, thereby killing the cancer cells and arresting tumor growth.[reviewed in 27] According to this theory, another consequence of lysosome disruption is stimulation of the immune system.




Laboratory/Animal/Preclinical Studies

On the basis of standard laboratory tests and animal models used to screen anticancer drugs, there is little evidence to support a specific cancer-killing ability for laetrile. These investigations used numerous cultured cell lines and tumor models, and they explored the following issues: 1) whether laetrile, given alone or in combination with other substances, exhibits anticancer activity of any kind; 2) the toxic effects associated with laetrile treatment; 3) the location of laetrile breakdown in the body and how this breakdown occurs; and 4) the route(s) of excretion for laetrile and its breakdown products.

Animal studies of laetrile have used rodents,[20,41-51] dogs,[10,52 reviewed in 3] rabbits,[reviewed in 3] and a cat.[10] Early work led to the hypothesis that enzymes were necessary to release cyanide from amygdalin. When high levels of these enzymes were present, symptoms of cyanide poisoning were more pronounced.[20, reviewed in 3] In two studies sponsored by the National Cancer Institute (NCI) and published in 1975, various rodent cancers (osteogenic sarcoma, melanoma, carcinosarcoma, lung carcinoma, and leukemia) were transplanted into rats and mice.[41,42] In both studies, the animals were treated with intraperitoneal injections of amygdalin, with or without the enzyme beta-glucosidase. None of the solid tumors or leukemias investigated responded to amygdalin at any dose tested. No statistically significant increase in animal survival was observed in any of the treatment groups. Similar results were obtained in another study using human breast and colon cancer cells implanted into mice (xenograft models).[51] Amygdalin at every dose level tested produced no response either as a single agent or in combination with beta-glucosidase. However, it was discovered that animals experienced more side effects when beta-glucosidase was given concurrently (at the same time) with amygdalin than with amygdalin alone.[41,42]

Additional cell culture and animal studies involving more than a dozen other tumor models have been published.[20,28,36,43,44,46,47,49,50,53-55] In one study, preliminary findings by one of the principal investigators that amygdalin inhibited the growth of primary tumors and the incidence of lung metastases in mice bearing spontaneous (not treatment-induced) mammary adenocarcinomas could not be confirmed.[43] However, positive results were obtained in four studies.[36,50,53,55]

In the first of these studies, amygdalin enhanced the antitumor activity of a combination of enzymes and vitamin A in mice bearing spontaneous mammary adenocarcinomas.[50] The amygdalin was given by intramuscular injection, the vitamin A was administered orally through a feeding tube, and the enzymes were injected into and around tumor masses. No anticancer activity was observed when amygdalin was given alone.

In the second study, white blood cells and prostate cancer specimens were used to investigate the potential of amygdalin to stimulate the immune system.[53] The researchers found that amygdalin caused a statistically significant increase in the ability of a patient's white blood cells to adhere to his own prostate cancer cells, suggesting some immune system boosting potential for amygdalin.

The third study investigated the ability of amygdalin and beta-glucosidase to indirectly sensitize the hypoxic (oxygen-starved) cells at the center of a tumor to the lethal effects of gamma irradiation.[36] Cells at the periphery (outer edge) of a tumor are more sensitive to gamma irradiation because they are not oxygen deprived. Radiation kills cells, in part, by splitting molecules, including oxygen molecules, to form free radicals, which are highly reactive chemicals that can damage DNA and other important cellular components. It has been proposed that, by inhibiting oxygen uptake by peripheral tumor cells, more oxygen will diffuse to the hypoxic cells, thereby increasing their sensitivity to radiation. In this study, beta-glucosidase was used to break amygdalin down to release cyanide, with the cyanide inhibiting oxygen uptake by peripheral tumor cells. Presumably, cyanide uptake by interior tumor cells is less than that of cells located at a tumor's periphery. Spheres of tumor cells created in the laboratory and tumor slices were used in the study. The investigators found that amygdalin and beta-glucosidase could act as indirect radiation sensitizers of hypoxic tumor cells. It should be noted, however, that independent confirmation of this positive finding has not been published in a peer-reviewed, scientific journal. A major hurdle in the application of this technique to animals and humans is the development of a method for delivering a sufficient amount of cyanide to tumors without causing substantial systemic or regional toxicity.

In the fourth study, cultured human bladder cancer cells were treated with amygdalin alone or a combination of amygdalin and an antibody that was coupled (chemically) to beta-glucosidase.[55] The target for this antibody was the glycoprotein (a protein with sugar molecules attached) MUC1. Aberrant forms of MUC1 are produced and displayed at high levels on the outside of several types of cancer cells, including bladder cancer cells. In this study, amygdalin alone was not very effective in killing the bladder cancer cells, but its cell-killing ability was 36-times greater in the presence of the antibody-enzyme complex. There are two possible explanations for this increase in cell-killing ability. The first is that antibody-enzyme complexes bound via MUC1 produce high rates of amygdalin breakdown at the cell surface. This breakdown leads to high local production of cyanide, which is quickly taken up by the cells and kills them. The second explanation is that antibody-enzyme complexes bound to the cells are internalized, thereby increasing the intracellular concentration of beta-glucosidase. Increased beta-glucosidase activity inside a cell would result in increased breakdown of amygdalin taken up by it, as well as increased cyanide production and cell death. These two potential mechanisms are not mutually exclusive. In another experiment, the researchers cultured bladder cancer cells in the presence of human brain tumor cells, which do not express MUC1. When this co-culture was treated with amygdalin and the antibody-enzyme complex, the bladder cancer cells were killed selectively. In view of the mechanisms proposed above, this result is not surprising, since the bladder cancer cells and the brain tumor cells in this co-culture formed homogeneous colonies (colonies that contained exclusively bladder cancer cells or brain tumor cells). Conceivably, selective killing of some types of human cancer cells might be achievable through application of this method; however, these positive results must be confirmed independently, and the effectiveness of this approach in animal models must be demonstrated before its use in humans can be considered.

The toxicity of laetrile appears to be dependent on the route of administration. Oral administration is associated with much greater toxicity than intravenous, intraperitoneal, or intramuscular injection.[20,45,52,56, reviewed in 16,31,48,49] As noted previously (History section), most mammalian cells contain only trace amounts of the enzyme beta-glucosidase;[34] however, this enzyme is present in gastrointestinal tract bacteria and in many food plants.[reviewed in 3,21,23,30,45,48] Two studies have specifically examined the role of intestinal bacteria in the breakdown of orally administered amygdalin.[38,48] In one study, rats bred and raised under germ-free conditions and rats bred and raised under normal conditions were given oral amygdalin. The germ-free rats exhibited no side effects from the compound, and their blood concentrations of cyanide were indistinguishable from those of untreated rats. In contrast, many of the rats with normal quantities of intestinal bacteria showed signs of cyanide poisoning (e.g., lethargy and convulsions), and they had high levels of cyanide in their blood. In the second study, rats were either treated or not treated with the antibiotic neomycin before being given oral amygdalin.[45] In this study, urinary excretion of detoxified cyanide (i.e., thiocyanate) was measured. The amount of urinary thiocyanate was 40-times higher in rats that had not been given the antibiotic, indicating that more amygdalin had been broken down in animals with normal amounts of intestinal bacteria. In humans, as in rats, substantial breakdown of amygdalin occurs in the intestines; however, little breakdown of either intravenously or intramuscularly delivered amygdalin occurs in humans, with most of the intact compound eventually excreted in urine.[23,57]




Human/Clinical Studies

Laetrile has been used as an anticancer treatment in humans worldwide.[reviewed in 10] Although many anecdotal reports and case reports are available, findings from only two clinical trials [8,56] have been published. No controlled clinical trial (a trial including a comparison group that receives no additional treatment, a placebo, or another treatment) of laetrile has ever been conducted.

Case reports and reports of case series have provided little evidence to support laetrile as an anticancer treatment.[26,9,31,32,58,reviewed in 10] The absence of a uniform documentation of cancer diagnosis, the use of conventional therapies in combination with laetrile, and variations in the dose and duration of laetrile therapy complicate evaluation of the data. In a case series published in 1962,[31] findings from ten patients with various types of metastatic cancer were reported. These patients had been treated with a wide range of doses of intravenous LaetrileŽ (total dose range, 9 to 133 grams). Pain relief (reduction or elimination) was the primary benefit reported. Some objective responses (responses that are measured rather than based on opinion), such as decreased adenopathy (swollen lymph nodes) and decreased tumor size, were noted. Information on prior or concurrent therapy was provided; however, patients were not followed long-term to determine whether the benefits continued after treatment was stopped. Another case series that was published in 1953 included 44 cancer patients and found no evidence of objective response that could be attributed to laetrile.[29] Most patients with reported cancer regression in this series received recent or concurrent radiation therapy or chemotherapy. Thus, it is impossible to determine which treatment produced the positive results.

Benzaldehyde, which is one of laetrile's breakdown products, has also been tested for anticancer activity in humans. Two clinical series reported a number of responses to benzaldehyde in patients with advanced cancer for whom standard therapy had failed.[18,19] In one series, 19 complete responses and 10 partial responses were reported among 57 patients who had received either oral or rectal beta-cyclodextrin benzaldehyde; however, precise response durations were specified for only two of the patients.[18] Another series by the same investigators used 4,6-benzylidene- alpha-D-glucose, which is an intravenous formulation of benzaldehyde.[19] In this series, seven complete responses and 29 partial responses were reported among 65 patients, with response durations ranging from 1.5 to 27 months. No toxicity was associated with either preparation of benzaldehyde, and it was reported that the responses persisted as long as treatment was continued. Almost all of the patients in these two series had been treated previously with chemotherapy or radiation therapy, but the elapsed time before the initiation of benzaldehyde treatment was not disclosed.

In 1978, the NCI requested case reports from practitioners who believed their patients had benefited from laetrile treatment.[59] Ninety-three cases were submitted, and 67 were considered evaluable for response. An expert panel concluded that two of the 67 patients had complete responses and that four others had partial responses while using laetrile.[7] On the basis of these six responses, the NCI agreed to sponsor phase I and phase II clinical trials.

The phase I study was designed to test the doses, routes of administration, and the schedule of administration judged representative of those used by laetrile practitioners.[56] The study involved six cancer patients. The investigators found that intravenous and oral amygdalin showed minimal toxicity under the conditions evaluated; however, two patients who ate raw almonds while undergoing oral treatment developed symptoms of cyanide poisoning.

The phase II study was conducted in 1982 and was designed to test the types of cancer that might benefit from laetrile treatment.[8] The majority of patients had breast, colon, or lung cancer. To be eligible for the trial, patients had to be in good general condition (not totally disabled or near death), and they must not have received any other cancer therapy for at least one month before treatment with amygdalin. Amygdalin, evaluated for potency and purity by the NCI,[60] was administered intravenously for 21 days, followed by oral maintenance therapy, utilizing doses and procedures similar to those evaluated in the phase I study. Vitamins and pancreatic enzymes were also administered as part of a metabolic therapy program that included dietary changes to restrict the use of caffeine, sugar, meats, dairy products, eggs, and alcohol. A small subset of patients received higher-dose amygdalin therapy and higher doses of some vitamins as part of the trial. Patients were followed until there was definite evidence of cancer progression, elevated blood cyanide levels, or severe clinical deterioration. Among 175 evaluable patients, only one patient met the criteria for response. This patient, who had gastric carcinoma with cervical lymph node metastasis, experienced a partial response that was maintained for 10 weeks while on amygdalin therapy. Fifty-four percent of patients had measurable disease progression at the end of the intravenous course of treatment, and all patients had progression seven months after completing intravenous therapy. Seven percent of patients reported an improvement in performance status (ability to work or to perform routine daily activities) at some time during therapy, and 20 percent claimed symptomatic relief. In most patients, these benefits did not persist. Blood cyanide levels were not elevated after intravenous amygdalin treatment; however, they were elevated after oral therapy.[8]

On the basis of this phase II study, NCI concluded that no further investigation of laetrile was warranted.[61] However, several concerns have been expressed about the study.[reviewed in 5]

Variations in commercial preparations of laetrile from Mexico, the primary supplier, have been documented.[60,62] Incorrect product labels have been found, and samples contaminated with bacteria and other substances have been identified.[60,62] When a comparison was made of products manufactured in the United States and Canada, differences in chemical composition were noted, and neither product was effective in killing cultured human cancer cells.[28]




Adverse Effects

The side effects associated with laetrile treatment mirror the symptoms of cyanide poisoning. Cyanide is a neurotoxin that can cause nausea and vomiting, headache,[reviewed in 1] dizziness,[8, reviewed in 15] cyanosis (bluish discoloration of the skin due to oxygen-deprived hemoglobin in the blood), liver damage,[63,64] hypotension (abnormally low blood pressure),[31,reviewed in 1,3] ptosis (droopy upper eyelid),[65,66] ataxic neuropathies (difficulty walking due to damaged nerves),[67] fever,[65, reviewed in 3] mental confusion, coma, and death.[reviewed in 23,31,56] Oral laetrile causes more severe side effects than injected laetrile. These side effects can be potentiated (increased) by the concurrent administration of raw almonds or crushed fruit pits, eating fruits and vegetables that contain beta-glucosidase (e.g., celery, peaches, bean sprouts, carrots),[20,52,64,reviewed in 15,21] or taking high doses of vitamin C.[64,68,reviewed in 1]




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. Separate levels of evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and scientific strength of the treatment outcomes (i.e., endpoints) measured. The resulting two scores are then combined to produce an overall score. A table showing the levels of evidence scores for qualifying human studies cited in this summary is presented below. For an explanation of the scores and 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.

Laetrile/Amygdalin Summary: Reference Numbers and the Corresponding Levels of Evidence

Reference Number Statistical Strength of Study Design Strength of Endpoints Measured Combined Score
8 3iii ­ Nonconsecutive Case Series Diii ­ Indirect Surrogates -- Tumor Response Rate 3iiiDiii
18 3iii ­ Nonconsecutive Case Series Diii ­ Indirect Surrogates -- Tumor Response Rate 3iiiDiii
19 3iii ­ Nonconsecutive Case Series Diii ­ Indirect Surrogates -- Tumor Response Rate 3iiiDiii
29 4 ­ Best Case Series Diii ­ Indirect Surrogates -- Tumor Response Rate 4Diii
31 4 ­ Best Case Series Diii ­ Indirect Surrogates -- Tumor Response Rate 4Diii
32 4 ­ Best Case Series Diii ­ Indirect Surrogates -- Tumor Response Rate 4Diii
56 3iii ­ Nonconsecutive Case Series Diii ­ Indirect Surrogates -- Tumor Response Rate 3iiiDiii



Glossary of Terms



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

adenopathy: Large or swollen lymph glands.

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.

animal model: An animal with a disease either the same as or like a disease in humans. Animal models are 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.

antibiotic: A drug used to treat infections caused by bacteria and other microorganisms.

antibody: A type of protein produced by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies disable antigens directly. Others make the antigen more vulnerable to destruction by white blood cells.

ataxia: Loss of muscle coordination.

benzaldehyde: A colorless oily liquid used as a flavoring agent and to make dyes, perfumes, and pharmaceuticals. Benzaldehyde is chemically related to benzene.

carcinosarcoma: A malignant tumor that is a mixture of carcinoma (cancer of epithelial tissue, which is skin and tissue that lines or covers the internal organs) and sarcoma (cancer of connective tissue, such as bone, cartilage, and fat).

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).

cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus.

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.

complete response: The disappearance of all signs of cancer. Also called a complete remission.

concurrent therapy: A treatment that is given at the same time as another.

controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all.

cultured cell line: Cells of a single type that have been grown in the laboratory for several generations (cell divisions).

cultured cells: Animal or human cells that are grown in the laboratory.

cyanogenic glucoside: A plant compound that contains sugar and produces cyanide.

cyanosis: Blue colored skin caused by too little oxygen in the blood.

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

diagnosis: The process of identifying a disease by the signs and symptoms.

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

evaluable patients: Patients whose response to a treatment can be measured because enough information has been collected.

free radicals: Highly reactive chemicals that often contain oxygen and are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. Free radicals can damage important cellular molecules such as DNA or lipids or other parts of the cell.

gamma irradiation: A type of radiation therapy that uses gamma radiation. Gamma radiation is a type of high-energy radiation that is different from x-rays.

gastric: Having to do with the stomach.

gastrointestinal tract: The stomach and intestines.

germ-free: Free of bacteria, disease-causing viruses, and other organisms that can cause infection.

glucose: Sugar.

glycoprotein: A protein that has sugar molecules attached to it.

hydrolysis: A chemical reaction that uses water to break down a compound.

hypotension: Abnormally low blood pressure.

hypoxic: Having too little oxygen.

intestinal: Relating to the intestines.

intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. People have a large intestine and a small intestine. Also called the bowel.

intracellular: Inside a cell.

intramuscular: IM. Within or into muscle.

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

intravenous: IV. Into a vein.

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).

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

maintenance therapy: Treatment that is given to help extend the benefit of previous therapy. Maintenance therapy is often given to reduce the risk of relapse in persons whose cancer is in remission.

metabolic: Having to do with metabolism.

metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme.

metabolic therapy: Treatment to correct changes in metabolism that can be caused by disease.

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.

metastatic: Having to do with metastasis.

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.

molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms.

nasal: By or having to do with the nose.

neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease.

neurotoxin: A substance that is poisonous to nerve tissue.

objective response: A measurable response.

oral: By or having to do with the mouth.

organism: A living entity, such as an animal, a plant, a bacterium, or a fungus.

osteogenic sarcoma: A malignant tumor of the bone. Also called osteosarcoma.

pancreas: A glandular organ located in the abdomen. It makes pancreatic juices, which contain enzymes that aid in digestion, and it produces several hormones, including insulin. The pancreas is surrounded by the stomach, intestines, and other organs.

pancreatic: Having to do with the pancreas.

pancreatic enzymes: A group of proteins secreted by the pancreas which aid in the digestion of food.

partial response: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial remission.

phase I trial: Phase I trials are the first step in testing a new treatment in humans. These studies test the best way to give a new treatment (for example, by mouth, intravenous infusion, or injection), and the best dose. The drug is usually given in progressively higher doses to determine the highest dose that does not cause harmful side effects. Because little is known about the possible risks and benefits of treatments being tested, phase I trials usually include only a limited number of patients who have not been helped by other known treatments.

phase II trial: Phase II trials focus on learning whether the new treatment has an anticancer effect (for example, whether it shrinks a tumor, or improves blood test results), and whether it is effective for a particular type of cancer.

primary tumor: The original tumor.

progression: An increase in scope or severity of a disease.

ptosis: Drooping of the upper eyelid.

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.

rectal: By or having to do with the rectum, which is the last 8 to 10 inches of the large intestine ending at the anus.

regional: In oncology, describes the body area right around a tumor.

regression: A decrease in the extent or size of cancer.

response: In medicine, an improvement related to treatment.

symptomatic: Having to do with the symptoms of disease or its treatment.

systemic: Affecting the entire body.

urinary: Having to do with urine or the organs of the body that produce and get rid of urine.

white blood cell: Refers to cells in the immune system that help the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others.

xenograft: The cells of one species transplanted to another species.




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For More Information

For more information on complementary and alternative therapies, contact the NIH National Center for Complementary and Alternative Medicine (NCCAM):


NCCAM Clearinghouse
Post Office Box 8218
Silver Spring, MD 20907-8218
TTY/TDY: 1-888-644-6226 (toll free)


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