Purpose of This PDQ Summary
Overview
General Information
History
Laboratory/Animal/Preclinical Studies
Human/Clinical Studies
Adverse Effects
Overall Level of Evidence for Laetrile/Amygdalin
Changes to This Summary (12/04/2007)
More Information

Purpose of This PDQ Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the use of laetrile as a treatment for cancer. The summary is reviewed regularly and updated as necessary by the PDQ Cancer Complementary and Alternative Medicine Editorial Board ¹.

Information about the following is included in this summary:

• A brief history of laetrile research.
• Possible side effects of laetrile use.

This summary is intended as a resource to inform and assist clinicians and other health professionals who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Some of the reference citations in the summary are accompanied by a level of evidence designation. These designations are intended to help the readers assess the strength of the evidence supporting the use of specific interventions or treatment strategies. The PDQ Cancer Complementary and Alternative Medicine Editorial Board uses a formal evidence ranking system ² in developing its level of evidence designations. These designations should not be used as a basis for reimbursement determinations.

This summary is also available in a patient version ³, which is written in less technical language.

Overview

This complementary and alternative medicine (CAM) information summary provides 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.

This summary contains the following key information:

• Laetrile is another name for the chemical amygdalin, which is found in the pits of many fruits and in numerous plants.
• Cyanide is thought to be the main anticancer component of laetrile.
• Laetrile was first used as a cancer treatment in Russia in 1845, and in the United States in the 1920s.
• Laetrile has shown little anticancer activity in animal studies and no anticancer activity in human clinical trials.
• Laetrile is not approved for use in the United States.
• Inappropriate advertisement of laetrile as a cancer treatment has resulted in a US Food and Drug Administration (FDA) investigation that culminated in charges and conviction of one distributor.

Many of the medical and scientific terms used in the summary are hypertext linked (at first use in each section) to the NCI Dictionary ⁴, which is oriented toward nonexperts. When a linked term is clicked, a definition will appear in a separate window. All linked terms and their corresponding definitions will appear in a glossary in the printable version of the summary.

Reference citations in some PDQ CAM information summaries may include links to external Web sites that are operated by individuals or organizations for the purpose of marketing or advocating the use of specific treatments or products. These reference citations are included for informational purposes only. Their inclusion should not be viewed as an endorsement of the content of the Web sites or of any treatment or product by the PDQ Cancer CAM Editorial Board or the National Cancer Institute (NCI).

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 [1-6] 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 [2,7,8] 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.[9] Reviewed in [10]

In the United States, researchers must file an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA) to conduct 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 [3,11,12] and because there were questions about how the proposed study was to be conducted. Reviewed in [13] Laetrile supporters viewed this reversal as an attempt by the US 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 US Supreme Court overturned decisions by the lower courts, thereby reaffirming the FDA’s position that drugs must be proven to be both safe and effective before widespread public use. Reviewed in [2,14] As a result, the use of laetrile as a cancer therapy or as a treatment for any other medical condition is not approved in the United States, but the compound continues to be manufactured and administered as an anticancer therapy, primarily in Mexico. Inappropriate advertisement of laetrile as a cancer treatment has resulted in an FDA investigation that culminated in charges and conviction of one distributor.[15]

Although the names laetrile, Laetrile, and amygdalin are often used interchangeably, they are not the same product. The chemical composition of US-patented Laetrile (mandelonitrile-beta-glucuronide), a semisynthetic 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 [16,17] Mandelonitrile, which contains cyanide, is a structural component of both products. Reviewed in [16] It has been proposed that cyanide is the active cancer-killing ingredient in laetrile, but 2 other breakdown products of amygdalin—prunasin (which is similar in structure to Laetrile) and benzaldehyde —may also be cancer cell inhibitors.[18-21] 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 in this summary; 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 [22] Reviewed in [23,24] 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 [18,23] Relatively little breakdown to yield cyanide occurs when laetrile is injected. Reviewed in [7,23] Administration schedules and the length of treatment in animal models and humans vary widely.

References

1. Howard-Ruben J, Miller NJ: Unproven methods of cancer management. Part II: Current trends and implications for patient care. Oncol Nurs Forum 11 (1): 67-73, 1984 Jan-Feb.  [PUBMED Abstract]
   
   
2. Curt GA: Unsound methods of cancer treatment. Princ Pract Oncol Updates 4 (12): 1-10, 1990. 
   
   
3. Dorr RT, Paxinos J: The current status of laetrile. Ann Intern Med 89 (3): 389-97, 1978.  [PUBMED Abstract]
   
   
4. Calabrese EJ: Possible adverse side effects from treatment with laetrile. Med Hypotheses 5 (9): 1045-9, 1979.  [PUBMED Abstract]
   
   
5. The laetrile controversy. In: Moss RW: The Cancer Industry: The Classic Expose on the Cancer Establishment. Brooklyn, NY: First Equinox Press, 1996, pp 131-52. 
   
   
6. Laetrile at Sloan-Kettering: a case study. In: Moss RW: The Cancer Industry: The Classic Expose on the Cancer Establishment. Brooklyn, NY: First Equinox Press, 1996, pp 153-86. 
   
   
7. Lerner IJ: Laetrile: a lesson in cancer quackery. CA Cancer J Clin 31 (2): 91-5, 1981 Mar-Apr.  [PUBMED Abstract]
   
   
8. Ellison NM, Byar DP, Newell GR: Special report on Laetrile: the NCI Laetrile Review. Results of the National Cancer Institute's retrospective Laetrile analysis. N Engl J Med 299 (10): 549-52, 1978.  [PUBMED Abstract]
   
   
9. Moertel CG, Fleming TR, Rubin J, et al.: A clinical trial of amygdalin (Laetrile) in the treatment of human cancer. N Engl J Med 306 (4): 201-6, 1982.  [PUBMED Abstract]
   
   
10. Ross WE: Unconventional cancer therapy. Compr Ther 11 (9): 37-43, 1985.  [PUBMED Abstract]
    
    
11. Lewis JP: Laetrile. West J Med 127 (1): 55-62, 1977.  [PUBMED Abstract]
    
    
12. Unproven methods of cancer management. Laetrile. CA Cancer J Clin 22 (4): 245-50, 1972 Jul-Aug.  [PUBMED Abstract]
    
    
13. Rosen GM, Shorr RI: Laetrile: end play around the FDA. A review of legal developments. Ann Intern Med 90 (3): 418-23, 1979.  [PUBMED Abstract]
    
    
14. Curran WJ: Law-medicine notes. Laetrile for the terminally ill: Supreme Court stops the nonsense. N Engl J Med 302 (11): 619-21, 1980.  [PUBMED Abstract]
    
    
15. U.S. Department of Justice, United States Attorney -- Eastern District of New York.: President of Queens Firm Found Guilty of Criminal Contempt For Violating Court Order Not to Market Bogus Cancer Cure Over the Internet. Rockville, Md: U.S. Food and Drug Administration, 2003. Available online. ⁵ Last accessed May 2, 2006. 
    
    
16. Fenselau C, Pallante S, Batzinger RP, et al.: Mandelonitrile beta-glucuronide: synthesis and characterization. Science 198 (4317): 625-7, 1977.  [PUBMED Abstract]
    
    
17. Chandler RF, Anderson LA, Phillipson JD: Laetrile in perspective. Can Pharm J 117 (11): 517-20, 1984. 
    
    
18. Newmark J, Brady RO, Grimley PM, et al.: Amygdalin (Laetrile) and prunasin beta-glucosidases: distribution in germ-free rat and in human tumor tissue. Proc Natl Acad Sci U S A 78 (10): 6513-6, 1981.  [PUBMED Abstract]
    
    
19. Rauws AG, Olling M, Timmerman A: The pharmacokinetics of prunasin, a metabolite of amygdalin. J Toxicol Clin Toxicol 19 (8): 851-6, 1982.  [PUBMED Abstract]
    
    
20. Kochi M, Takeuchi S, Mizutani T, et al.: Antitumor activity of benzaldehyde. Cancer Treat Rep 64 (1): 21-3, 1980.  [PUBMED Abstract]
    
    
21. Kochi M, Isono N, Niwayama M, et al.: Antitumor activity of a benzaldehyde derivative. Cancer Treat Rep 69 (5): 533-7, 1985.  [PUBMED Abstract]
    
    
22. Gostomski FE: The effects of amygdalin on the Krebs-2 carcinoma and adult and fetal DUB(ICR) mice. [Abstract] Diss Abstr Int B 39 (5): 2075-B, 1978. 
    
    
23. Herbert V: Laetrile: the cult of cyanide. Promoting poison for profit. Am J Clin Nutr 32 (5): 1121-58, 1979.  [PUBMED Abstract]
    
    
24. Viehoever A, Mack H: Bio-chemistry of amygdalin (bitter, cyanogenetic principle from bitter almonds). Am J Pharm 107(Oct): 397-450, 1935. 
    
    

History

Amygdalin was first isolated in 1830 by 2 French chemists. Reviewed in [1,2] It was used as an anticancer agent in Russia as early as 1845, with positive results reported for the first patient treated. Reviewed in [3,4] Its first recorded use in the United States as a treatment for cancer occurred in the early 1920s. Reviewed in [5] 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 Laetrile. Reviewed in [1,6,7]

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 ⁶), cyanide is believed to be the main cancer-killing ingredient in laetrile.[8,9] 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 [1,7,8,10,11] Cyanide can also be produced from prunasin, which is a less-than-complete breakdown product of amygdalin. Reviewed in [1,8]

Four different theories have been advanced to explain the anticancer activity of laetrile. The first of these incorporates elements of the trophoblastic theory of cancer, 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, would give rise to eggs or sperm), some of which become dispersed throughout the body during embryonic development and, therefore, are not confined to the testes or 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.[12] Reviewed in [13-17] 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 down the modified compound, 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 2 enzymes. Reviewed in [10,13,18-20] 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.[21,22]

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 [1,5,13,15,18,23,24] Evidence from laboratory studies demonstrates that this theory cannot be supported. As noted previously, normal cells and cancer cells contain similar amounts of rhodanese.[21] Furthermore, most types of mammalian cells contain only small traces of beta-glucosidase,[22] and this enzyme has not been detected in tumor samples [8,25] or in human blood.[5] 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 [18,26-28] 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 [29,30]

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 [15] According to this theory, another consequence of lysosome disruption is stimulation of the immune system.

References

1. Dorr RT, Paxinos J: The current status of laetrile. Ann Intern Med 89 (3): 389-97, 1978.  [PUBMED Abstract]
   
   
2. Viehoever A, Mack H: Bio-chemistry of amygdalin (bitter, cyanogenetic principle from bitter almonds). Am J Pharm 107(Oct): 397-450, 1935. 
   
   
3. The laetrile controversy. In: Moss RW: The Cancer Industry: The Classic Expose on the Cancer Establishment. Brooklyn, NY: First Equinox Press, 1996, pp 131-52. 
   
   
4. Laetrile at Sloan-Kettering: a case study. In: Moss RW: The Cancer Industry: The Classic Expose on the Cancer Establishment. Brooklyn, NY: First Equinox Press, 1996, pp 153-86. 
   
   
5. Curt GA: Unsound methods of cancer treatment. Princ Pract Oncol Updates 4 (12): 1-10, 1990. 
   
   
6. Fenselau C, Pallante S, Batzinger RP, et al.: Mandelonitrile beta-glucuronide: synthesis and characterization. Science 198 (4317): 625-7, 1977.  [PUBMED Abstract]
   
   
7. Chandler RF, Anderson LA, Phillipson JD: Laetrile in perspective. Can Pharm J 117 (11): 517-20, 1984. 
   
   
8. Newmark J, Brady RO, Grimley PM, et al.: Amygdalin (Laetrile) and prunasin beta-glucosidases: distribution in germ-free rat and in human tumor tissue. Proc Natl Acad Sci U S A 78 (10): 6513-6, 1981.  [PUBMED Abstract]
   
   
9. Rauws AG, Olling M, Timmerman A: The pharmacokinetics of prunasin, a metabolite of amygdalin. J Toxicol Clin Toxicol 19 (8): 851-6, 1982.  [PUBMED Abstract]
   
   
10. Ross WE: Unconventional cancer therapy. Compr Ther 11 (9): 37-43, 1985.  [PUBMED Abstract]
    
    
11. Ames MM, Moyer TP, Kovach JS, et al.: Pharmacology of amygdalin (laetrile) in cancer patients. Cancer Chemother Pharmacol 6 (1): 51-7, 1981.  [PUBMED Abstract]
    
    
12. Krebs ET Jr, Krebs ET Sr, Beard HH: The unitarian or trophoblastic thesis of cancer. Med Rec 163 (7): 149-74, 1950. 
    
    
13. Ellison NM: Unproven methods of cancer therapy. Drug Ther (NY) 10(July): 73-82, 1980. 
    
    
14. Navarro MD: The Philippine experience in the early detection and chemotherapy of cancer. St Tomas J Med 25 (3): 125-33, 1970. 
    
    
15. Greenberg DM: The case against laetrile: the fraudulent cancer remedy. Cancer 45 (4): 799-807, 1980.  [PUBMED Abstract]
    
    
16. Levi L, French WN, Bickis IJ, et al.: Laetrile: a study of its physicochemical and biochemical properties. Can Med Assoc J 92: 1057-61, 1965. 
    
    
17. Cancer Commission of the California Medical Association.: The treatment of cancer with "laetriles". Calif Med 78 (4): 320-26, 1953. 
    
    
18. Unproven methods of cancer management. Laetrile. CA Cancer J Clin 22 (4): 245-50, 1972 Jul-Aug.  [PUBMED Abstract]
    
    
19. Navarro MD: Five years experience with laetrile therapy in advanced cancer. Acta Unio Int Contr Cancrum 15(suppl 1): 209-21, 1959. 
    
    
20. Morrone JA: Chemotherapy of inoperable cancer: preliminary report of 10 cases treated with laetrile. Exp Med Surg 20: 299-308, 1962. 
    
    
21. Gal EM, Fung FH, Greenberg DM: Studies on the biological action of malononitriles, II: distribution of rhodanese (transulfurase) in the tissues of normal and tumor-bearing animals and the effect of malononitriles thereon. Cancer Res 12: 574-79, 1952. 
    
    
22. Conchie J, Findlay J, Levvy GA: Mammalian glycosidases: distribution in the body. Biochem J 71: 318-25, 1959. 
    
    
23. Herbert V: Laetrile: the cult of cyanide. Promoting poison for profit. Am J Clin Nutr 32 (5): 1121-58, 1979.  [PUBMED Abstract]
    
    
24. Scott PJ: Laetrile and cancer quackery problems. Cancer Forum 5 (2): 93-97, 1981. 
    
    
25. Biaglow JE, Durand RE: The enhanced radiation response of an in vitro tumour model by cyanide released from hydrolysed amygdalin. Int J Radiat Biol Relat Stud Phys Chem Med 33 (4): 397-401, 1978.  [PUBMED Abstract]
    
    
26. Lerner IJ: Laetrile: a lesson in cancer quackery. CA Cancer J Clin 31 (2): 91-5, 1981 Mar-Apr.  [PUBMED Abstract]
    
    
27. Lerner IJ: The whys of cancer quackery. Cancer 53 (3 Suppl): 815-9, 1984.  [PUBMED Abstract]
    
    
28. Shils ME, Hermann MG: Unproved dietary claims in the treatment of patients with cancer. Bull N Y Acad Med 58 (3): 323-40, 1982.  [PUBMED Abstract]
    
    
29. Young VR, Newberne PM: Vitamins and cancer prevention: issues and dilemmas. Cancer 47 (5 Suppl): 1226-40, 1981.  [PUBMED Abstract]
    
    
30. Jukes TH: Laetrile struggles. Nature 263 (5578): 543, 1976. 
    
    

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,[1-12] dogs,[13,14] Reviewed in [15] rabbits, Reviewed in [15] and a cat.[13] 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.[1] Reviewed in [15] In 2 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.[2,3] 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).[12] Amygdalin at every dose level tested produced no response either as a single agent or in combination with beta-glucosidase. It was discovered that animals experienced more side effects when beta-glucosidase was given concurrently (at the same time) with amygdalin, however, than with amygdalin alone.[2,3]

Additional cell culture and animal studies involving more than a dozen other tumor models have been published.[1,4,5,7,8,10,11,16-20] 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.[4] However, positive results were obtained in 4 studies.[11,17,18,20]

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.[11] 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.[18] 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.[17] 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 down amygdalin 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.[20] 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 2 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 2 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 coculture 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 coculture 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.[1,6,14,21] Reviewed in [9,10,22,23] As noted previously (History ⁷), most mammalian cells contain only trace amounts of the enzyme beta-glucosidase;[24] however, this enzyme is present in gastrointestinal tract bacteria and in many food plants. Reviewed in [6,9,15,25-27] Two studies have specifically examined the role of intestinal bacteria in the breakdown of orally administered amygdalin.[9,28] 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.[6] 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.[26,29]

References

1. Gostomski FE: The effects of amygdalin on the Krebs-2 carcinoma and adult and fetal DUB(ICR) mice. [Abstract] Diss Abstr Int B 39 (5): 2075-B, 1978. 
   
   
2. Wodinsky I, Swiniarski JK: Antitumor activity of amygdalin MF (NSC-15780) as a single agent and with beta-glucosidase (NSC-128056) on a spectrum of transplantable rodent tumors. Cancer Chemother Rep 59 (5): 939-50, 1975 Sep-Oct.  [PUBMED Abstract]
   
   
3. Laster WR Jr, Schabel FM Jr: Experimental studies of the antitumor activity of amygdalin MF (NSC-15780) alone and in combination with beta-glucosidase (NSC-128056). Cancer Chemother Rep 59 (5): 951-65, 1975 Sep-Oct.  [PUBMED Abstract]
   
   
4. Stock CC, Tarnowski GS, Schmid FA, et al.: Antitumor tests of amygdalin in transplantable animal tumor systems. J Surg Oncol 10 (2): 81-8, 1978.  [PUBMED Abstract]
   
   
5. Menon MM, Bhide SV: Perinatal carcinogenicity of isoniazid (INH) in Swiss mice. J Cancer Res Clin Oncol 105 (3): 258-61, 1983.  [PUBMED Abstract]
   
   
6. Newton GW, Schmidt ES, Lewis JP, et al.: Amygdalin toxicity studies in rats predict chronic cyanide poisoning in humans. West J Med 134 (2): 97-103, 1981.  [PUBMED Abstract]
   
   
7. Hill GJ 2nd, Shine TE, Hill HZ, et al.: Failure of amygdalin to arrest B16 melanoma and BW5147 AKR leukemia. Cancer Res 36 (6): 2102-7, 1976.  [PUBMED Abstract]
   
   
8. Lea MA, Koch MR: Effects of cyanate, thiocyanate, and amygdalin on metabolite uptake in normal and neoplastic tissues of the rat. J Natl Cancer Inst 63 (5): 1279-83, 1979.  [PUBMED Abstract]
   
   
9. Carter JH, McLafferty MA, Goldman P: Role of the gastrointestinal microflora in amygdalin (laetrile)-induced cyanide toxicity. Biochem Pharmacol 29 (3): 301-4, 1980.  [PUBMED Abstract]
   
   
10. Khandekar JD, Edelman H: Studies of amygdalin (laetrile) toxicity in rodents. JAMA 242 (2): 169-71, 1979.  [PUBMED Abstract]
    
    
11. Manner HW, DiSanti SJ, Maggio MI, et al.: Amygdalin, vitamin A and enzyme induced regression of murine mammary adenocarcinomas. J Manipulative Physiol Ther 1 (4): 246-8, 1978. 
    
    
12. Ovejera AA, Houchens DP, Barker AD, et al.: Inactivity of DL-amygdalin against human breast and colon tumor xenografts in athymic (nude) mice. Cancer Treat Rep 62 (4): 576-8, 1978.  [PUBMED Abstract]
    
    
13. Lewis JP: Laetrile. West J Med 127 (1): 55-62, 1977.  [PUBMED Abstract]
    
    
14. Schmidt ES, Newton GW, Sanders SM, et al.: Laetrile toxicity studies in dogs. JAMA 239 (10): 943-7, 1978.  [PUBMED Abstract]
    
    
15. Dorr RT, Paxinos J: The current status of laetrile. Ann Intern Med 89 (3): 389-97, 1978.  [PUBMED Abstract]
    
    
16. Levi L, French WN, Bickis IJ, et al.: Laetrile: a study of its physicochemical and biochemical properties. Can Med Assoc J 92: 1057-61, 1965. 
    
    
17. Biaglow JE, Durand RE: The enhanced radiation response of an in vitro tumour model by cyanide released from hydrolysed amygdalin. Int J Radiat Biol Relat Stud Phys Chem Med 33 (4): 397-401, 1978.  [PUBMED Abstract]
    
    
18. Bhatti RA, Ablin RJ, Guinan PD: Tumour-associated directed immunity in prostatic cancer: effect of amygdalin. IRCS Med Sci Biochem 9 (1): 19, 1981. 
    
    
19. Koeffler HP, Lowe L, Golde DW: Amygdalin (Laetrile): effect on clonogenic cells from human myeloid leukemia cell lines and normal human marrow. Cancer Treat Rep 64 (1): 105-9, 1980.  [PUBMED Abstract]
    
    
20. Syrigos KN, Rowlinson-Busza G, Epenetos AA: In vitro cytotoxicity following specific activation of amygdalin by beta-glucosidase conjugated to a bladder cancer-associated monoclonal antibody. Int J Cancer 78 (6): 712-9, 1998.  [PUBMED Abstract]
    
    
21. Moertel CG, Ames MM, Kovach JS, et al.: A pharmacologic and toxicological study of amygdalin. JAMA 245 (6): 591-4, 1981.  [PUBMED Abstract]
    
    
22. Newmark J, Brady RO, Grimley PM, et al.: Amygdalin (Laetrile) and prunasin beta-glucosidases: distribution in germ-free rat and in human tumor tissue. Proc Natl Acad Sci U S A 78 (10): 6513-6, 1981.  [PUBMED Abstract]
    
    
23. Navarro MD: Five years experience with laetrile therapy in advanced cancer. Acta Unio Int Contr Cancrum 15(suppl 1): 209-21, 1959. 
    
    
24. Conchie J, Findlay J, Levvy GA: Mammalian glycosidases: distribution in the body. Biochem J 71: 318-25, 1959. 
    
    
25. Herbert V: Laetrile: the cult of cyanide. Promoting poison for profit. Am J Clin Nutr 32 (5): 1121-58, 1979.  [PUBMED Abstract]
    
    
26. Ames MM, Moyer TP, Kovach JS, et al.: Pharmacology of amygdalin (laetrile) in cancer patients. Cancer Chemother Pharmacol 6 (1): 51-7, 1981.  [PUBMED Abstract]
    
    
27. Unproven methods of cancer management. Laetrile. CA Cancer J Clin 22 (4): 245-50, 1972 Jul-Aug.  [PUBMED Abstract]
    
    
28. Shils ME, Hermann MG: Unproved dietary claims in the treatment of patients with cancer. Bull N Y Acad Med 58 (3): 323-40, 1982.  [PUBMED Abstract]
    
    
29. Ames MM, Kovach JS, Flora KP: Initial pharmacologic studies of amygdalin (laetrile) in man. Res Commun Chem Pathol Pharmacol 22 (1): 175-85, 1978.  [PUBMED Abstract]
    
    

Human/Clinical Studies

Laetrile has been used as an anticancer treatment in humans worldwide. Reviewed in [1] Although many anecdotal reports and case reports are available, findings from only 2 clinical trials [2,3] 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.[4-8] Reviewed in [1] 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,[6] findings from 10 patients with various types of metastatic cancer were reported. These patients had been treated with a wide range of doses of intravenous Laetrile (total dose range, 9-133 g). 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.[9] 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.[10,11] 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 2 of the patients.[10] Another series by the same investigators used 4,6-benzylidene-alpha-D-glucose, which is an intravenous formulation of benzaldehyde.[11] In this series, 7 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 2 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 National Cancer Institute (NCI) requested case reports from practitioners who believed their patients had benefitted from laetrile treatment.[12] Ninety-three cases were submitted, and 67 were considered evaluable for response. An expert panel concluded that 2 of the 67 patients had complete responses and that 4 others had partial responses while using laetrile.[13] On the basis of these 6 responses, 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.[3] The study involved 6 cancer patients. The investigators found that intravenous and oral amygdalin showed minimal toxicity under the conditions evaluated; however, 2 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.[2] Most 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 1 month before treatment with amygdalin. Amygdalin, evaluated for potency and purity by NCI,[14] 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 1 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 7 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.[2]

Variations in commercial preparations of laetrile from Mexico, the primary supplier, have been documented.[14,15] Incorrect product labels have been found, and samples contaminated with bacteria and other substances have been identified.[14,15] 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.[16]

References

1. Lewis JP: Laetrile. West J Med 127 (1): 55-62, 1977.  [PUBMED Abstract]
   
   
2. Moertel CG, Fleming TR, Rubin J, et al.: A clinical trial of amygdalin (Laetrile) in the treatment of human cancer. N Engl J Med 306 (4): 201-6, 1982.  [PUBMED Abstract]
   
   
3. Moertel CG, Ames MM, Kovach JS, et al.: A pharmacologic and toxicological study of amygdalin. JAMA 245 (6): 591-4, 1981.  [PUBMED Abstract]
   
   
4. Navarro MD: The Philippine experience in the early detection and chemotherapy of cancer. St Tomas J Med 25 (3): 125-33, 1970. 
   
   
5. Ross WE: Unconventional cancer therapy. Compr Ther 11 (9): 37-43, 1985.  [PUBMED Abstract]
   
   
6. Navarro MD: Five years experience with laetrile therapy in advanced cancer. Acta Unio Int Contr Cancrum 15(suppl 1): 209-21, 1959. 
   
   
7. Morrone JA: Chemotherapy of inoperable cancer: preliminary report of 10 cases treated with laetrile. Exp Med Surg 20: 299-308, 1962. 
   
   
8. Brown WE, Wood CD, Smith AN: Sodium cyanide as a cancer chemotherapeutic agent: laboratory and clinical studies. Am J Obstet Gynecol 80 (5): 907-18, 1960. 
   
   
9. Cancer Commission of the California Medical Association.: The treatment of cancer with "laetriles". Calif Med 78 (4): 320-26, 1953. 
   
   
10. Kochi M, Takeuchi S, Mizutani T, et al.: Antitumor activity of benzaldehyde. Cancer Treat Rep 64 (1): 21-3, 1980.  [PUBMED Abstract]
    
    
11. Kochi M, Isono N, Niwayama M, et al.: Antitumor activity of a benzaldehyde derivative. Cancer Treat Rep 69 (5): 533-7, 1985.  [PUBMED Abstract]
    
    
12. Newell GR, Ellison NM: Ethics and designs: laetrile trials as an example. Cancer Treat Rep 64 (2-3): 363-5, 1980 Feb-Mar.  [PUBMED Abstract]
    
    
13. Ellison NM, Byar DP, Newell GR: Special report on Laetrile: the NCI Laetrile Review. Results of the National Cancer Institute's retrospective Laetrile analysis. N Engl J Med 299 (10): 549-52, 1978.  [PUBMED Abstract]
    
    
14. Davignon JP, Trissel LA, Kleinman LM: Pharmaceutical assessment of amygdalin (Laetrile) products. Cancer Treat Rep 62 (1): 99-104, 1978.  [PUBMED Abstract]
    
    
15. Davignon JP: Contaminated laetrile: a health hazard. N Engl J Med 297 (24): 1355-6, 1977.  [PUBMED Abstract]
    
    
16. Levi L, French WN, Bickis IJ, et al.: Laetrile: a study of its physicochemical and biochemical properties. Can Med Assoc J 92: 1057-61, 1965. 
    
    

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,[2] Reviewed in [3] cyanosis (bluish discoloration of the skin due to oxygen-deprived hemoglobin in the blood), liver damage,[4,5] hypotension (abnormally low blood pressure),[6] Reviewed in [1,7] ptosis (droopy upper eyelid),[8,9] ataxic neuropathies (difficulty walking due to damaged nerves),[10] fever,[8] Reviewed in [7] mental confusion, coma, and death. Reviewed in [6,11,12] 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),[5,13,14] Reviewed in [3,15] or taking high doses of vitamin C.[5,16] Reviewed in [1]

References

1. Howard-Ruben J, Miller NJ: Unproven methods of cancer management. Part II: Current trends and implications for patient care. Oncol Nurs Forum 11 (1): 67-73, 1984 Jan-Feb.  [PUBMED Abstract]
   
   
2. Moertel CG, Fleming TR, Rubin J, et al.: A clinical trial of amygdalin (Laetrile) in the treatment of human cancer. N Engl J Med 306 (4): 201-6, 1982.  [PUBMED Abstract]
   
   
3. Chandler RF, Anderson LA, Phillipson JD: Laetrile in perspective. Can Pharm J 117 (11): 517-20, 1984. 
   
   
4. Leor R, Michaeli J, Brezis M, et al.: Laetrile intoxication and hepatic necrosis: a possible association. South Med J 79 (2): 259-60, 1986.  [PUBMED Abstract]
   
   
5. Lee M, Berger HW, Givre HL, et al.: Near fatal laetrile intoxication: complete recovery with supportive treatment. Mt Sinai J Med 49 (4): 305-7, 1982 Jul-Aug.  [PUBMED Abstract]
   
   
6. Navarro MD: Five years experience with laetrile therapy in advanced cancer. Acta Unio Int Contr Cancrum 15(suppl 1): 209-21, 1959. 
   
   
7. Dorr RT, Paxinos J: The current status of laetrile. Ann Intern Med 89 (3): 389-97, 1978.  [PUBMED Abstract]
   
   
8. Smith FP, Butler TP, Cohan S, et al.: Laetrile toxicity: a report of two patients. Cancer Treat Rep 62 (1): 169-71, 1978.  [PUBMED Abstract]
   
   
9. Vizel M, Oster MW: Ocular side effects of cancer chemotherapy. Cancer 49 (10): 1999-2002, 1982.  [PUBMED Abstract]
   
   
10. Kalyanaraman UP, Kalyanaraman K, Cullinan SA, et al.: Neuromyopathy of cyanide intoxication due to "laetrile" (amygdalin). A clinicopathologic study. Cancer 51 (11): 2126-33, 1983.  [PUBMED Abstract]
    
    
11. Ames MM, Moyer TP, Kovach JS, et al.: Pharmacology of amygdalin (laetrile) in cancer patients. Cancer Chemother Pharmacol 6 (1): 51-7, 1981.  [PUBMED Abstract]
    
    
12. Moertel CG, Ames MM, Kovach JS, et al.: A pharmacologic and toxicological study of amygdalin. JAMA 245 (6): 591-4, 1981.  [PUBMED Abstract]
    
    
13. Gostomski FE: The effects of amygdalin on the Krebs-2 carcinoma and adult and fetal DUB(ICR) mice. [Abstract] Diss Abstr Int B 39 (5): 2075-B, 1978. 
    
    
14. Schmidt ES, Newton GW, Sanders SM, et al.: Laetrile toxicity studies in dogs. JAMA 239 (10): 943-7, 1978.  [PUBMED Abstract]
    
    
15. Herbert V: Laetrile: the cult of cyanide. Promoting poison for profit. Am J Clin Nutr 32 (5): 1121-58, 1979.  [PUBMED Abstract]
    
    
16. Calabrese EJ: Conjoint use of laetrile and megadoses of ascorbic acid in cancer treatment: possible side effects. Med Hypotheses 5 (9): 995-7, 1979.  [PUBMED Abstract]
    
    

Overall Level of Evidence for Laetrile/Amygdalin

To assist readers in evaluating the results of human studies of complementary and alternative medicine (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 level of evidence analysis, a study must:

• Be published in a peer-reviewed scientific journal.
• Report on a therapeutic outcome or outcomes, such as tumor response, improvement in survival, or measured improvement in quality of life.
• 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, refer to Levels of Evidence for Human Studies of Cancer Complementary and Alternative Medicine ².

References

1. Moertel CG, Fleming TR, Rubin J, et al.: A clinical trial of amygdalin (Laetrile) in the treatment of human cancer. N Engl J Med 306 (4): 201-6, 1982.  [PUBMED Abstract]
   
   
2. Kochi M, Takeuchi S, Mizutani T, et al.: Antitumor activity of benzaldehyde. Cancer Treat Rep 64 (1): 21-3, 1980.  [PUBMED Abstract]
   
   
3. Kochi M, Isono N, Niwayama M, et al.: Antitumor activity of a benzaldehyde derivative. Cancer Treat Rep 69 (5): 533-7, 1985.  [PUBMED Abstract]
   
   
4. Cancer Commission of the California Medical Association.: The treatment of cancer with "laetriles". Calif Med 78 (4): 320-26, 1953. 
   
   
5. Navarro MD: Five years experience with laetrile therapy in advanced cancer. Acta Unio Int Contr Cancrum 15(suppl 1): 209-21, 1959. 
   
   
6. Morrone JA: Chemotherapy of inoperable cancer: preliminary report of 10 cases treated with laetrile. Exp Med Surg 20: 299-308, 1962. 
   
   
7. Moertel CG, Ames MM, Kovach JS, et al.: A pharmacologic and toxicological study of amygdalin. JAMA 245 (6): 591-4, 1981.  [PUBMED Abstract]
   
   

Changes to This Summary (12/04/2007)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Purpose of This PDQ Summary ⁹

Added this new section.

More Information

Additional Information about CAM Therapies

• The National Center for Complementary and Alternative Medicine ¹⁰ (NCCAM).
• The National Cancer Institute Office of Cancer Complementary and Alternative Medicine ¹¹ (OCCAM).
• CAM on PubMed ¹², a special subset of the PubMed scientific literature database created through a partnership between NCCAM and the National Library of Medicine.

About PDQ

• PDQ® - NCI's Comprehensive Cancer Database ¹³

  Full description of the NCI PDQ database.

Other PDQ Summaries

• PDQ® Cancer Information Summaries: Adult Treatment ¹⁴

  Treatment options for adult cancers.

• PDQ® Cancer Information Summaries: Pediatric Treatment ¹⁵

  Treatment options for childhood cancers.

• PDQ® Cancer Information Summaries: Supportive and Palliative Care ¹⁶

  Side effects of cancer treatment, management of cancer-related complications and pain, and psychosocial concerns.

• PDQ® Cancer Information Summaries: Screening/Detection (Testing for Cancer) ¹⁷

  Tests or procedures that detect specific types of cancer.

• PDQ® Cancer Information Summaries: Prevention ¹⁸

  Risk factors and methods to increase chances of preventing specific types of cancer.

• PDQ® Cancer Information Summaries: Genetics ¹⁹

  Genetics of specific cancers and inherited cancer syndromes, and ethical, legal, and social concerns.

• PDQ® Cancer Information Summaries: Complementary and Alternative Medicine ²⁰

  Information about complementary and alternative forms of treatment for patients with cancer.

Important:

This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

Glossary Terms

Cancer that begins in cells that line certain internal organs and that have gland-like (secretory) properties.

Large or swollen lymph glands.

A substance found in the pits of many fruits such as apricots and papayas, and in other foods. It has been tried in some countries as a treatment for cancer, but it has not been shown to work in clinical studies. Amygdalin is not approved for use in the United States. Also called laetrile.

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.

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.

A laboratory experiment using animals to study the development and progression of diseases. Animal studies also test how safe and effective new treatments are before they are tested in people.

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

A type of protein made by plasma cells (a type of white blood cell) in response to an antigen (foreign substance). Each antibody can bind to only one 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 destroy antigens directly. Others make it easier for white blood cells to destroy the antigen.

Having to do with stopping abnormal cell growth.

Loss of muscle coordination.

A large group of single-cell microorganisms. Some cause infections and disease in animals and humans. The singular of bacteria is bacterium.

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

The organ that stores urine.

Glandular organ located on the chest. The breast is made up of connective tissue, fat, and breast tissue that contains the glands that can make milk. Also called mammary gland.

A term for diseases in which abnormal cells divide without control. Cancer cells can invade nearby tissues and can spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord.

Cancer that begins in the skin or in tissues that line or cover internal organs.

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).

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).

A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment.

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

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.

Treatment with drugs that kill cancer cells.

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

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called a clinical study.

The longest part of the large intestine, which is a tube-like organ connected to the small intestine at one end and the anus at the other. The colon removes water and some nutrients and electrolytes from partially digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus.

Cancer that forms in the tissues of the colon (the longest part of the large intestine). Most colon cancers are adenocarcinomas (cancers that begin in cells that make and release mucus and other fluids).

CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices generally are not considered standard medical approaches. Standard treatments go through a long and careful research process to prove they are safe and effective, but less is known about most types of CAM. CAM may include dietary supplements, megadose vitamins, herbal preparations, special teas, acupuncture, massage therapy, magnet therapy, spiritual healing, and meditation. Also called CAM.

The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. Also called complete remission.

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

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

A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment.

A human, plant, or animal cell that has been adapted to grow in the laboratory. Cultured cells may be used to diagnose infections, to test new drugs, and in research.

Cells of a single type (human, animal, or plant) that have been adapted to grow continuously in the laboratory and are used in research.

A plant compound that contains sugar and produces cyanide.

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

In medicine, a shortage of a substance (such as a vitamin or mineral) needed by the body.

DNA. The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called DNA.

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

The process of identifying a disease, such as cancer, from its signs and symptoms.

The amount of medicine taken, or radiation given, at one time.

Having to do with an embryo, which is an early stage in the development of a plant or animal.

In clinical trials, an event or outcome that can be measured objectively to determine whether the intervention being studied is beneficial. The endpoints of a clinical trial are usually included in the study objectives. Some examples of endpoints are survival, improvements in quality of life, relief of symptoms, and disappearance of the tumor.

A protein that speeds up chemical reactions in the body.

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

FDA. An agency in the U.S. federal government whose mission is to protect public health by making sure that food, cosmetics, and nutritional supplements are safe to use and truthfully labeled. The Food and Drug Administration also makes sure that drugs, medical devices, and equipment are safe and effective, and that blood for transfusions and transplant tissue are safe. Also called FDA.

A highly reactive chemical that often contains oxygen and is produced when molecules are split to give products that have unpaired electrons (a process called oxidation). Free radicals can damage important cellular molecules such as DNA or lipids or other parts of the cell.

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

Having to do with the stomach.

The stomach and intestines. The gastrointestinal tract is part of the digestive system, which also includes the salivary glands, mouth, esophagus, liver, pancreas, gallbladder, and rectum.

A reproductive cell of the body. Germ cells are egg cells in females and sperm cells in males.

Free of bacteria, viruses, and other organisms that can cause infection and disease.

A type of sugar; the chief source of energy for living organisms.

A protein that has sugar molecules attached to it.

A unit of weight in the metric system. One gram is equal to one thousandth of a kilogram and is approximately 30-times less than an ounce.

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

Abnormally low blood pressure.

Having too little oxygen.

The complex group of organs and cells that defends the body against infections and other diseases.

Taking into the body by mouth.

Use of a syringe and needle to push fluids or drugs into the body; often called a "shot."

Having to do with the intestines.

The long, tube-shaped organ in the abdomen that completes the process of digestion. The intestine has two parts, the small intestine and the large intestine. Also called the bowel.

Inside a cell.

IM. Within or into muscle. Also called IM.

Injection into muscle.

IP. Within the peritoneal cavity (the area that contains the abdominal organs). Also called IP.

Into or within a vein. Intravenous usually refers to a way of giving a drug or other substance through a needle or tube inserted into a vein. Also called I.V.

In clinical trials, refers to a drug (including a new drug, dose, combination, or route of administration) or procedure that has undergone basic laboratory testing and received approval from the U.S. Food and Drug Administration (FDA) to be tested in human subjects. A drug or procedure may be approved by the FDA for use in one disease or condition, but be considered investigational in other diseases or conditions. Also called experimental.

A researcher in a clinical trial or clinical study.

Research done in a laboratory. These studies may use test tubes or animals to find out if a drug, procedure, or treatment is likely to be useful. Laboratory studies take place before any testing is done in humans.

A substance found in the pits of many fruits such as apricots and papayas, and in other foods. It has been tried in some countries as a treatment for cancer, but it has not been shown to work in clinical studies. Laetrile is not approved for use in the United States. Also called amygdalin.

Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream.

A ranking system used to describe the strength of the results measured in a clinical trial or research study. The design of the study (such as a case report for an individual patient or a randomized double-blinded controlled clinical trial) and the endpoints measured (such as survival or quality of life) affect the strength of the evidence.

A large organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile.

One of a pair of organs in the chest that supplies the body with oxygen, and removes carbon dioxide from the body.

Cancer that forms in tissues of the lung, usually in the cells lining air passages. The two main types are small cell lung cancer and non-small cell lung cancer. These types are diagnosed based on how the cells look under a microscope.

A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Lymph nodes filter lymph (lymphatic fluid), and they store lymphocytes (white blood cells). They are located along lymphatic vessels. Also called lymph gland.

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

Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission.

Cancerous. Malignant tumors can invade and destroy nearby tissue and spread to other parts of the body.

Having to do with the breast.

A form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other pigmented tissues, such as in the eye or in the intestines.

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

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

The total of all chemical changes that take place in a cell or an organism. These changes make energy and the materials needed for growth, reproduction, and maintaining health. They also help get rid of toxic substances.

The spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a “metastatic tumor” or a “metastasis.” The metastatic tumor contains cells that are like those in the original (primary) tumor. The plural form of metastasis is metastases (meh-TAS-tuh-SEEZ).

Having to do with metastasis, which is the spread of cancer from one part of the body to another.

The smallest particle of a substance that has all of the physical and chemical properties of that substance. Molecules are made up of one or more atoms. If they contain more than one atom, the atoms 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.

The National Cancer Institute, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. The National Cancer Institute conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the National Cancer Institute Web site at http://www.cancer.gov. Also called NCI.

A feeling of sickness or discomfort in the stomach that may come with an urge to vomit. Nausea is a side effect of some types of cancer therapy.

A nerve problem that causes pain, numbness, tingling, swelling, or muscle weakness in different parts of the body. It usually begins in the hands or feet and gets worse over time. Neuropathy may be caused by physical injury, infection, toxic substances, disease (such as cancer, diabetes, kidney failure, or malnutrition), or drugs, including anticancer drugs. Also called peripheral neuropathy.

A substance that is poisonous to nerve tissue.

A clinical study that includes some, but not all, of the eligible patients identified by the researchers during the study registration period. This type of study does not usually have a control group.

Not harmful or destructive.

A measurable response.

By or having to do with the mouth.

A living thing, such as an animal, a plant, a bacterium, or a fungus.

A cancer of the bone that usually affects the large bones of the arm or leg. It occurs most commonly in young people and affects more males than females. Also called osteosarcoma.

One of a pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus.

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.

Having to do with the pancreas.

A protein secreted by the pancreas that aids in the digestion of food.

A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. Also called partial remission.

PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, complementary and alternative medicine, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information, and more specific information about PDQ, can be found on the NCI's Web site at http://www.cancer.gov/cancertopics/pdq. Also called Physician Data Query.

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 dose is usually increased a little at a time in order to find the highest dose that does not cause harmful side effects. Because little is known about the possible risks and benefits of the treatments being tested, phase I trials usually include only a small number of patients who have not been helped by other treatments.

A study to test whether a new treatment has an anticancer effect (for example, whether it shrinks a tumor or improves blood test results) and whether it works against a certain type of cancer.

An inactive substance or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.

Research using animals to find out if a drug, procedure, or treatment is likely to be useful. Preclinical studies take place before any testing in humans is done.

The original tumor.

In medicine, the course of a disease, such as cancer, as it becomes worse or spreads in the body.

Cancer that forms in tissues of the prostate (a gland in the male reproductive system found below the bladder and in front of the rectum). Prostate cancer usually occurs in older men.

Drooping of the upper eyelid.

The overall enjoyment of life. Many clinical trials assess the effects of cancer and its treatment on the quality of life. These studies measure aspects of an individual’s sense of well-being and ability to carry out various activities.

The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called radiotherapy and irradiation.

By or having to do with the rectum. The rectum is the last several inches of the large intestine and ends at the anus.

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

A decrease in the size of a tumor or in the extent of cancer in the body.

In medicine, an improvement related to treatment.

A problem that occurs when treatment affects healthy tissues or organs. Some common side effects of cancer treatment are fatigue, pain, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores.

An abnormal mass of tissue that usually does not contain cysts or liquid areas. Solid tumors may be benign (not cancerous), or malignant (cancerous). Different types of solid tumors are named for the type of cells that form them. Examples of solid tumors are sarcomas, carcinomas, and lymphomas. Leukemias (cancers of the blood) generally do not form solid tumors.

The male reproductive cell, formed in the testicle. A sperm unites with an egg to form an embryo.

In medicine, treatment that experts agree is appropriate, accepted, and widely used. Health care providers are obligated to provide patients with standard therapy. Also called standard of care or best practice.

Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. Also called significant.

Adding nutrients to the diet.

Having to do with symptoms, which are signs of a condition or disease.

Affecting the entire body.

One of two egg-shaped glands found inside the scrotum that produce sperm and male hormones. Also called a testicle.

Having to do with treating disease and helping healing take place.

Treatment.

A group or layer of cells that work together to perform a specific function.

Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects.

The replacement of tissue with tissue from the person’s own body or from another person.

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancerous), or malignant (cancerous). Also called neoplasm.

Cells, tissues, or animals used to study the development and progression of cancer, and to test new treatments before they are given to humans. Animals with transplanted human tumors or other tissues are called xenograft models.

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

A key nutrient that the body needs in small amounts to grow and stay strong. Examples are vitamins A, C, and E.

One of several vitamins that the body needs in small amounts to function and stay healthy. Vitamin A is needed for vision, bone growth, reproduction, growth of epithelium (cells that line the internal and external surfaces of the body), and fighting infections. It is fat-soluble (can be stored in the body’s fatty tissue). Foods with vitamin A include fish oils and liver, egg yolks, and whole milk dairy products from animals. It also can be made in the body from a substance found in fruits and vegetables such as cantaloupes, carrots, spinach, and sweet potatoes. Vitamin A is being studied in the prevention and treatment of some types of cancer. Also called retinol.

To eject some or all of the contents of the stomach through the mouth.

Refers to a blood cell that does not contain hemoglobin. White blood cells include lymphocytes, neutrophils, eosinophils, macrophages, and mast cells. These cells are made by bone marrow and help the body fight infections and other diseases. Also called WBC.

The cells of one species transplanted to another species.