The case of the LAETRILE – Vitamin B17

Is Laetrile or Vitamin B17 an effective therapy for cancer?

 

Partially tract from “A Commonweal Working Paper”, by Vivekan Don Flint and Michael Lerner Research Assistance: Melanie Smith, October, 1997,

The most enduring legacy of the meteoric rise of Laetrile to a place of preeminence among unconventional therapies for cancer during the 1970s may well be sociological and political, rather then medical in nature. Laetrile spawned a popular movement for freedom of choice in health care decisions spanning the ideological spectrum that probably has not been seen in this country since the time of Harry Hoxsey. Though it had been in use for at least 25 years as a therapy for cancer, it is estimated that at any given time during the mid-1970s, 70,000 people were using Laetrile as a cancer treatment, for pain control or as a preventive measure.(1421)

In the debate over broader philosophical and political issues, the critical question for cancer patients, whether or not Laetrile is an effective therapy for cancer, was largely overshadowed, though clearly Laetrile has not lived up to the expectations of many of its most ardent advocates.

According to journalist Michael Culbert, D.Sc., founding member of the Laetrile advocacy group Committee for Freedom of Choice in Cancer Therapy, Inc.: I decided very early that the issue was neither scientific nor medical but political. And that issue was–is–simple: What right does the state have, or should it have, to intervene in the medical decisions between a patient and his doctor, particularly if that patient is dying of a „terminal“ disease for which there is no known, or guaranteed cure? (1422)

Ralph Moss, a key figure in the Laetrile controversy in the 1970s, has been a leading critic of the cancer orthodoxy, as well as the political and economic forces he believes drive it, since leaving his position as Assistant Director of Public Affairs at Memorial Sloan-Kettering Cancer Center (MSKCC) in 1977. Moss was fired for aligning himself publicly with a group of MSKCC employees who believed the public was being given inaccurate information on the outcome of animal studies of Laetrile’s effectiveness. Moss provides a detailed account of the Laetrile controversy and his experience at MSKCC in his book The Cancer Industry. Moss states the medical issue this way: ”Laetrilists are not just advocating a single substance but, like the advocates of other unorthodox therapies, are proposing a new kind of treatment for the patient’s body and mind”.

There is apparently an irreconcilable difference between laetrilists and orthodox doctors in how they understand cancer. Since the time of John Hunter (1728-1793), orthodox physicians have tended to see cancer as a localized disease that, as Hunter said, „only produces local effects.“ Such a disease would therefore be curable through localized means–for example, removing the growth through surgery.

…Experiments in this century, and particularly in the past thirty years, have suggested that the body has natural immune mechanisms against cancer analogous to those that function in microbial infections. The corollary of this view is that cancer can be controlled by enhancing the body’s normal immune functions, which orthodox methods tend to destroy. (1420)

The typical „metabolic therapy“ often advocated by proponents of Laetrile includes megadoses of vitamins A and C, minerals such as selenium, and enzymes, particularly pancreatic enzymes. And, in order to free these enzymes to act upon cancer cells, practitioners often recommend limiting intake of animal protein. Alcohol, coffee, soft drinks and processed foods may also be proscribed.(1423)

The early 1970s saw growing numbers of patients seeking out Laetrile as a cancer therapy and it was during this time that the Laetrile became the focus of a large-scale political movement, as well. In June 1972, John Richardson, M.D., an Albany, California physician whose used Laetrile in his rapidly-expanding practice, was arrested for violating state laws intended to curtail its use. Richardson was a member of the conservative John Birch Society, and its membership rallied around the issue. The three trials of Richardson galvanized a national movement for freedom of choice in medical therapies, and the original Committee for Freedom of Choice in Medical Therapy, Inc. ballooned into a nationwide movement in all 50 states with a membership estimated at 20,000 to 50,000 members. (1424)

In July 1973, Dean Burke, while still working with the NCI, wrote to Congressman Robert A. Roe that Laetrile had been successful in NCI directed studies using the Lewis mouse lung cancer model while the agency consistently denied its efficacy (1425).

1975 was a pivotal year in the controversy over Laetrile. In that year a U.S. District Court judge barred the FDA from preventing patients from securing their own supplies of Laetrile from foreign sources. Later that same year, federal officials conducted a crackdown on the importation of Laetrile into this country. Sixteen people, including Robert Bradford, now affiliated with the American Biologics clinic in Tijuana, were arrested or indicted on charges of smuggling Laetrile from Mexico. The principles were eventually found guilty in a lengthy trial, though no prison time was meted out (1426).

The OTA also summarized the efforts by the NCI in the mid-1970s to obtain documented evidence of objective responses to Laetrile using an approach designed to collect information from individuals or practitioners who felt they had used Laetrile successfully in the treatment of cancer. The intention was not to determine rates of success, but rather to collect evidence of antitumor affect. The NCI sent nearly half a million letters to physicians, other health professionals and to pro-Laetrile groups asking for documented case histories of patients who had shown objective responses to Laetrile, with or without metabolic treatment, with a treatment period of at least 30 days, with a period of at least 30 days prior where no conventional treatment had been used.

Two hundred thirty patients responded with claims of objective response using Laetrile. Ninety-three of these gave permission for release of their medical records, and for 26 of these insufficient information was provided for review purposes. The final review was based on the remaining 67 cases. In an effort to avoid bias, twenty-six case histories of patients with similar cancers who received only conventional therapies were added to the Laetrile cases.

Summaries of the course of the disease without information about the therapy used were prepared for each patient and presented to a panel of 12 oncologists from outside the NCI. A group consensus was reached for each case after a discussion of the individuals reviews.

The panel determined that there were two complete remissions, four partial remissions and nine cases of stable disease. Thirty-five cases were of no value since they did not meet the original criteria for inclusion, and 11 had insufficient data upon which to judge responses. Despite the attempts to blind the panelists regarding Laetrile use, a higher than expected proportion answered correctly when asked to guess which patients had used Laetrile. Interestingly, the consensus for the six Laetrile-treated patients who were determined to have had partial or complete responses and for the three determined to have had increased disease-free survival, was that they had received conventional chemotherapy.

In their discussion of the review, the authors point out that the relatively small number of case submissions and loss of cases due to incomplete information left only a small number of evaluatable cases. Further: The patients treated with Laetrile were almost always given concomitant metabolic therapy…as well as general supportive-care measures such as improved diet, psychologic support and the unmeasurable ingredient of hope. This fact makes it difficult to attribute any tumor response to Laetrile alone (1427).

See: http://www.mednat.org/cancro/ELLISON_1427.pdf

Following this case review, the NCI sponsored phase I and II clinical trials, which were carried out at the Mayo Clinic. The phase I study gathered information about dosage and toxicity (1428) in preparation for the phase II study. One hundred seventy-eight patients with advanced cancers were treated with amygdalin according to a regimen designed to resemble „current Laetrile practice,“ which included a special diet and vitamin supplements. A subgroup of 14 patients with colorectal cancer was given a high-dose regimen of amygdalin and supplements resembling high-dose regimens used by some metabolic practitioners (http://fiocco59.altervista.org/nacci/Moertel%201982.pdf ) (1256)

All patients had disease for which no conventional therapy was available, though none were bedridden and all could eat normally. About a third of the patients had had no chemotherapy whatsoever, significant because of the claims of many practitioners that metabolic therapies are more effective in patients whose immune systems have not been damaged by chemotherapy.

The amygdalin, prepared from apricot pits by the NCI, was administered intravenously for 21 days, followed by continuous oral administration which was terminated with progression of the disease or severe clinical deterioration.

Three patients were taken off the regimen because of high blood levels of cyanide.

One of the 175 evaluable patients demonstrated a partial response (at least a 50 percent decrease in the size of the lesion); this response was transient, however. By the end of the three-week course of intravenous amygdalin, more than half of the patients demonstrated measurable disease progression. By seven months, all patients had progressive disease.

Median survival for the entire group was 4.8 months, a result similar to that of the 14 high-dose patients. The researchers found little evidence of symptom relief. Toxicities were generally mild when patients adhered to treatment schedules.

The authors concluded that the survival times of the patients appeared to be consistent with survival times of patients „receiving inactive treatment or no treatment“(1256). The OTA report notes that this comparison was not entirely valid, since the trial did not include a randomized control group and was not designed to determine if amygdalin caused moderate increases in lifespan or improvements in well-being or pain control (1429).

Laetrile supporters predictably criticized the study, claiming the material used was not Laetrile but a „degraded product.“(1430). The OTA Report counters that the Laetrile used was prepared according to one of several popular formulations in use at the time and that the regimen did correspond to current Laetrile practice (1431). American Biologics, then a California company with ties to the Committee for Freedom of Choice in Cancer Therapy, had offered to provide free Laetrile for the study and when the government refused the offer, the Committee unsuccessfully tried to block the trial, believing the test substance was not pure amygdalin, but a form that would not release cyanide (1432).

According to Culbert:

The „Laetrile clinical trial“…wound up being in essence a US government sponsored test of an uncertain Laetrile product whose application was in the hands of doctors and scientists known to be or assumed to be hostile to Laetrile, whose patients were anonymous, and the test results of which, being coded, could not be individually released or crosschecked.

Worse, the patients accepted for entry into the program were variously described as „terminal“ or beyond hope of cure by conventional means, yet not at the „final stage.“

The government [released] data on the test before the trial results were published as a kind of slide presentation…A Committee observer at the event was able to photograph a slide which showed that a significant number of test patients had remained „stable“ while on the injectable part of a program whose oral protocol, we had every reason to believe, was not strongly adhered to (and parts of which, as in suggested vitamin A levels) seemed not to have been followed at all. (1432)

The results of the trial published in the New England Journal of Medicine showed Laetrile to be ineffective as a cancer treatment, but Culbert and other Laetrile advocates believed the trial raised more questions than it answered: [D]epending on how the numbers were read, either a small majority or a large plurality of patients remained „stable“ while on the injectable part of the program, and only advanced into further disease after the 21 days of injections ceased. It later surfaced „anecdotally“ that at least one patient was urged not to continue on the program (claiming he had „done too well“). As a corollary, a preliminary test found amygdalin not to be toxic, at least in the ranges suggested for therapeutic use.(1432)

And, according to Richard Walters, Dr. James Cason of the University of California, Berkeley, analyzed the compound used in the Mayo Clinic study using infrared spectrophotometry and determined that it did not contain amygdalin at all (1433).

And in a charge often leveled at efforts to evaluate alternative therapies, opponents of the trial pointed out that 66 percent of the patients had received chemotherapy which they believed had severely damaged their immune systems and compromised their ability to respond to Laetrile.

Though it continues to be used at several clinics in Mexico and by practitioners in the states where it is legal, in the minds of many, the Mayo Clinic trial was the final word on Laetrile. But for Laetrile advocates, the scientific questions largely still unresolved, and there remains what seems to some to be abundant anecdotal evidence for the effectiveness of Laetrile. According to Culbert: There were too many doctors stepping forward with case histories…too many dissident scientists claiming there was some merit in the notion of anti-cancer efficacy from glycosidic compounds, and far, far too many „anecdotes“ from patients treated in Mexico or even within the USA to be able to claim the apricot kernel extract was totally without value…

[N]otable failures of Laetrile therapy got plenty of press attention, particularly if the failures came from the growing caseloads of Drs. Contreras and Richardson. Such negatives were indeed reported in gruesome detail–yet it was only an occasional journalist who dared contrast failures on vincristine, 5 FU, adriamycin, radiation and surgery, since somehow a failure on an orthodox modality was somehow less a failure than one on unorthodox therapy (1434).

In the political effort that had been spearheaded by the Committee for Freedom of Choice in Cancer Therapies, between 1976 and 1981, bills decriminalizing Laetrile or legalizing it outright were approved in 24 states. Bills passed twice in New York, but were vetoed each time. Such laws remain in 20 states (1435). According to Culbert: The Committee stuck to a single sweeping principle–that the issue was not so much freedom for Laetrile as it was freedom of informed consent in cancer therapy in general, for physician and patient…One observer after another joined the conceptual battle and usually remained clear on the separation of the issues of freedom of choice in medicine vs. the efficacy of Laetrile: by what stroke of logic or presumed vested interest does the state have the right to intervene in lifeand- death decisions between a physician and a patient, particularly when the patient is said to be „terminal,“ as with cancer? (1436)

Today, it is illegal to use Laetrile in states that do not have laws specifically allowing it. In 1977, a U.S. District Court judge ruled that the FDA had acted illegally in seizing shipments of Laetrile, and he enjoined the FDA from further seizures; that injunction was overturned in 1979. In a separate decision, a judge set up a system under which a patient could get Laetrile for personal use if a physician signed an affidavit that the individual was terminally ill, but his system was voided in 1987. As a result of these decisions, it is illegal to transport Laetrile across state lines or into the United States, even with a physician’s prescription.

Federal District Judge Luther Bohanon who established the affidavit system for Laetrile in 1977 offered his considered view of the controversy: Advocates of Laetrile’s use in cancer treatment include many highly educated and prominent doctors and scientists whose familiarity and practical experience with the substance vastly exceeds that of their detractors. To deem such advocacy „quackery“ distorts the serious issues posed by Laetrile’s prominence and requires disregarding considerable expertise mustered on the drug’s behalf.

While the record reveals an impressive consensus among the nation’s large medical and cancer-fighting institutions as to Laetrile’s ineffectualness, a disconcerting dearth of experience with the substance by such detractors is revealed…

The current debate is fierce. The issue appears largely unresolved as to Laetrile’s true effectiveness, in large part because FDA has prevented adequate testing on humans….

It is only when the substance is openly used, and its results carefully observed and fully reported that this controversy will be resolved. (1437)