Does Laetrile Work? Another Look at the Mayo Clinic Study (Moertel et al., 1982).

Abstract

Moertel et. al. (1992) studied the impact of laetrile on 172 cancer patients and concluded that it had no effect. The study used a mixture of natural and synthetic laetrile that laetrile experts consider to be minimally or not effective, followed an inflexible schedule of administration of laetrile injections, and involved patients "for which no standard treatment was known to be curative or to extend life expectancy." The study is informative, but the results do not support Moertel et. al.'s conclusion that further investigation or use of laetrile is not justified. Despite the widespread belief that Laetrile is ineffective against cancer, there have been only two large-scale clinical studies. I commented on the first study, 1,2 arguing that descriptions of this study in the professional literature give an overly pessimistic view of the efficacy of Laetrile. In the second clinical study, done at the Mayo clinic, Moertel et. al. studied 172 cancer patients “in good general condition” treated with Laetrile and an accompanying diet, and concluded that Laetrile had no effect. They concluded with the recommendation that “further investigation or clinical use of such therapy is not justified (p. 205). 3 The Mayo study has been widely cited and is considered by many to be definitive. When it appeared, Time Magazine ran an article with the title “Laetrlle flunks” with the subtitle “Test shows cancer quackery.” 4 The typical response of the profession is an article in the CA-A Cancer Journal for Physicians, “Unproven methods of cancer management,” which proclaimed that the Mayo study “showed unequivocally that Laetrile is ineffective for cancer therapy” (p. 190). 5 Laetrile supporters, however, have been vocal critics of the Mayo study. Soon after the study appeared, several letters to the editor commenting on Moertel et. al. appeared in the New England Journal of Medicine, and Charles Moertel, the first author of the Mayo study, responded, dealing with some of the criticisms but ignoring others, as we will see below. My commentary will deal with the following points, expanding on remarks made by critics of the Mayo study. The kind of Laetrile used. 1. The way the Laetrile was administered. 2. The use of terminal patients. 3. The interpretation of the results. 4. WHAT KIND OF LAETRILE? In his letter to the editor of the New England Journal of Medicine, Culbert notes that the Mayo study did not use pure amygdalin but a “degraded or decomposed form of it (the putative 'RS-epimer racemic mixture').” 6 The RS epimer racemic mixture is a mixture of natural amygdalin (R-amygdalin) and an isomer, an artificial form (referred to as the S-isomer, or isoamygdalin). Krebs strongly argues against the use of this kind of amygdalin, and maintains that this mixture is less than half as effective as the pure form (see the Appendix below for suggestive evidence that the Mayo mixture might have been even weaker). Krebs, in fact, points out that the mixture “caused unpredictable, often severe, reactions in our patients” and that “all of our successful therapeutic studies were conducted using only pure natural amygdalin” (p. 279). He even speculates that the mixture might be “carcinogenic or promote metastasis” (p. 298). 7 A number of other practitioners advise the use of “pure” amygdalin, 8 but the meaning of the word “pure” is unclear: Moertel et. al. also refer to the mixture they used as “pure Does Laetrile Work? Another Look at the Mayo Clinic Study (Moertel et al., 1982). 2 of 5 amygdalin” (p. 202). Moertel et. al. 3 defended the use of the mixture because it is the same as that provided “by a major Mexican manufacturer” citing an analysis done by Jee, Pont, Cheung, and Lim 9 of samples of Laetrile supplied by the National Cancer Institute. The samples Jee et. al. analyzed had been seized by US Customs as they were being transported illegally in the United States and were labeled as originating from Cyto Pharma de Mexico. According to its website, Cyto Pharma “was the first company to receive a license (under the direct supervision of Dr. Krebs which included his formula, process, technology and control methods) to produce Amigdalina (Amygdalin) ...” 10 This is a strange, considering Krebs' strong disapproval of the mixture which Jee et. al. reported finding in containers with Cyto Pharma's marking. The samples of injectable Laetrile Jee et. al. analyzed were indeed mixtures of natural and synthetic Laetrile but it is not clear that this was the kind of Laetrile used in studies of success reported in the professional literature. Clearly it would have been preferable if the Mayo researchers had contacted physicians who claimed success with Laetrile and had obtained “pure” Laetrile from them. ADMINISTRATION OF LAETRILE: DOSE AND DURATION Mayo researchers 3 claimed that the dose of laetrile given was sufficient, actually in excess of that provided to patients by Laetrile supporters, a total of approximately 150 grams by injection, which was followed with oral Laetrile (.5 g three times per day). The Mayo study used “a daily dose of 4.5 g per square meter of body-surface area” for 21 days. Using the Body Surface Area Calculator for medication doses (http://www.halls.md/body-surface-area/bsa.htm), this would mean that a 45 year old man 5' 9” weighing 175 pounds would get an injection of just under 9 grams per day, and a total dose of about 180 grams. A 45 year old 5' 4” woman weighing 140 pounds would receive a daily dose of about 7.5 grams, or a little under 160 grams in total. This dose of injected Laetrile appears to be more than sufficient and is consistent with previous practice: Krebs and Bouziane 11 gave their 12 patients from 34 to 235 grams. Marrone 12 reported an average total dosage of 46.2 grams (range 9 to 133). Binzel 13 generally administered a total of about 177 grams. Rodriguez, Pulido and Prince 14 administered between 54 to 72 grams. In all cases, oral Laetrile was also given, sometimes during the injection sequence, and always after. VARIABLE DURATION OF INJECTIONS There is, however, an important difference. In the Mayo study, Laetrile injections were given for three weeks, and then stopped, and oral Laetrile alone was used instead. The usual practice by Laetrile practitioners, however, is not to stop injections automatically after a given length of time: Rather, injections were continued until it appeared that the cancer was under control, and only then was oral Laetrile given for maintenance. The duration of treatment with injections in these studies varied according to the progress of the cancer. Moertel et. al., in contrast, mechanically switched from injection to oral Laetrile after three weeks. Navarro 15 writes that “Laetrile therapy may be discontinued after the Beard Anthrone test has become negative,” and makes it clear that Laetrile is administered by injection (p. 166). The average duration of treatment in Marrone 12 was 17.5 weeks, with some patients receiving injections for four to ten months (cases 6,7 and 8). Rodriguez et. al. 14 note that in patients “with severe persistence in the symptomology or recurrence” injections continued one to three days per week “until palliation was achieved or the treatment was considered to have failed” (p. 4, chart 1). This procedure was also reported in several case histories: Helen Curran reports that her doctor gave her intramuscular injections of laetrile every day until her cancer was in remission (p. 68). 16 Similarly, in the case of Joanne Wilkinson (in Griffen, p. 120), injections (3 grams) were continued three times per week for six months. 17 In addition, some practitioners continued Laetrile far longer than the Mayo clinics' 21 days as a general procedure: Krebs and Bouziane 11 kept all patients on a maintenance dose of 1 to 2 gram injections per week after “the base 30 grams” (p. 192). Richardson and Griffen 18 administered daily injections of 6-9 grams for 20 days, then three times per week for a month, twice a week for another month, and once a week for a year or longer (see p. 116), supplemented with oral Laetrile. Laetrile practioners also start using injections again if the cancer returned. Binzel's Case 6 13 was put back on Laetrile injections Does Laetrile Work? Another Look at the Mayo Clinic Study (Moertel et al., 1982). 3 of 5 because “she did not feel as well as she did while on them. She went back on some injections for a few months, and she felt much better” (p. 116) and then returned to taking only oral Laetrile. Binzel's Case 10 had been on tablets for two years, “without any problems” along with a nutritional program.” When the cancer returned years later, “She went back on her nutritional program again, except this time I added a series of intravenous Laetrile injections” (p. 118). Navarro 19 had stopped all therapy in one patient for two months (case B) but resumed injections when the Beard Anthrone test showed cancer was still present. Also, as noted earlier Rodriquez et. al. 14 used injections in cases of recurrence. In contrast, Mayo researchers 3 continued treatment until “definite evidence of progressive malignant disease or until severe clinical deterioration precluded further treatment and observation” (p. 202). In such cases, Laetrile practitioners would have presumably continued injections or would have returned to injections had they been stopped. USE OF TERMINAL PATIENTS The Mayo study 3 only included patients who were considered to be terminal, “for which no standard treatment was known to be curative or to extend life expectancy” (p. 201). As Bross 20 notes, these were patients who were not expected to benefit from any orthodox therapy. Bross concludes that “all that has been learned from the Laetrile study is that there is a class of patients whom no treatment – orthodox therapy or Laetrile – can help. This really tells us very little” (p. 118). In response to Bross, Moertel 21 claims that although the patients were terminal