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Laetrile/Amygdalin (PDQ®)

Health Professional Version
Last Modified: 02/05/2014

Human/Clinical Studies

Laetrile has been used as an anticancer treatment in humans worldwide.[1] Although many anecdotal reports and case reports are available, findings from only two 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.[1,4-8] 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 ten 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 ten 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.[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, 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 National Cancer Institute (NCI) requested case reports from practitioners who believed that 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 two of the 67 patients had complete responses and that four of the others had partial responses while using laetrile.[13] 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.[3] 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.[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 the 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 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 the patients had measurable disease progression at the end of the intravenous course of treatment, and all of the patients had disease progression 7 months after completing intravenous therapy. Seven percent of the 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. Treatment of cancer with laetriles; a report by the Cancer Commission of the California Medical Association. Calif Med 78 (4): 320-6, 1953.  [PUBMED Abstract]

  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 (20): 1057-61, 1965.