LAETRILE - Part 2
Critics of mainstream laetrile research have often noted that laetrile is rarely used alone, but more often part of a more comprehensive metabolic regimen. In 1978, Harold Manner, Ph.D., and colleagues conducted the first large scale experiment in animals using laetrile in combination with other supportive therapies. Manner, Chairman of the Department of Biology at Loyola University in Chicago, used a combination of vitamin A, Wobe Mugos enzymes and laetrile with 105 mice with breast tumors. Manner's results were dramatic: After 6-8 days an ulceration appeared at the tumor site. Within the ulceration was a puslike fluid. An examination of the fluid revealed dead malignant cells...The tumors gradually underwent complete regression in 75 of the experimental animals. This represented 89.3% of the total group. The remaining 9 animals showed partial regression. No attempts were made to determine increase in life span or changes in metastases.

Manner's results were greeted with skepticism by most researchers. Manner was criticized for presenting his results first to a public group- the National Health Federation--rather than to a scientific group, thus intentionally or unintentionally bypassing the peer review process. Manner responded that it would take years for the results to be reviewed and published and that hundreds of thousands of people would die needlessly in the meantime. He was also criticized for not testing laetrile, vitamin A and enzymes separately.

In a follow-up experiment, Manner studied 550 mice with spontaneous mammary tumors using laetrile injected intramuscularly, vitamin A, and digestive enzymes injected into and around the tumor mass. These were tested individually and in various combinations and the animals were observed for signs of tumor regression during a thirty day treatment period. No tumor regressions were observed in animals treated with laetrile alone, vitamin A alone, or both in combination. Tumor regressions were seen in the four treatment groups receiving digestive enzymes, and a few regressions were seen in the control group, as well. Fifty-two percent or more of the tumors regressed in the groups treated with enzymes alone, enzymes and vitamin A, enzymes and laetrile, and laetrile, enzymes and vitamin A in combination. The authors concluded that laetrile alone is "not effective in tumor regression," but that "76 percent of the tumors do completely regress" when all three substances are used in combination. The results were published in the Journal of Manipulative Physiological Therapies in 1978.

Manner's studies are viewed skeptically by most orthodox cancer researchers. For example, the authors of the Office of Technology report state that the observed effect seemed to result from "the immediate proteolytic effect of injecting digestive enzymes directly into tumor masses." Manner countered such criticism by pointing out that no attempt was ever made to replicate his research.

Manner subsequently took over the Cydel Hospital in Tijuana and renamed it the Manner Clinic, which continues to offer the "Manner cocktail" despite Manner's death in 1988.

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.

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 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.

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." 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.

Laetrile supporters predictably criticized the study, claiming the material used was not laetrile but a "degraded product." 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. 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.

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 cross-checked. 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.

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: Depending 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.

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.

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.

The potential toxicity of laetrile has consistently been cited as a serious issue by those in favor of regulation. CA - Cancer Journal for Clinicians cites several case reports describing serious or lethal cyanide toxicity from laetrile ingestion, some resulting from ingestion of laetrile by children and others in adults taking oral laetrile at the prescribed dose levels. The article asserts that cyanide toxicity is a risk only with oral ingestion of laetrile, since it is beta-glucosidase made by bacteria in the intestine decomposes amygdalin into cyanide; with intravenous laetrile, the standard treatment method, most is excreted in the urine without releasing cyanide, and so can have no therapeutic effect.

And according to a toxicity study by E.S. Schmidt published in the Journal of the American Medical Association, the danger of laetrile toxicity is enhanced if foods containing the enzyme beta-glucosidase are eaten along with oral laetrile, since the release of cyanide into the body is accelerated. Raw almonds and other nuts, bean and alfalfa sprouts, peaches, lettuce, celery and mushrooms are all sources of beta glucosidase. Common adverse effects found in the Mayo Clinic study of laetrile included nausea, headaches, vomiting and dizziness.

But Moss points out that the two or three documented deaths ascribed to accidental overdoses of laetrile occurred at a time when 50,000 to 100,000 patients were ingesting over one million grams of laetrile per month. Further, according to Moss, there are no case reports of any deaths or serious injuries resulting from laetrile injections.

Culbert also counters that reports of laetrile toxicity were deliberately exaggerated by opponents. He argues that virtually no laetrile-using physicians prescribed oral laetrile above the dose presumed useful therapeutically, 1.5 grams per day. Further, he argues that intravenous laetrile is considered non-toxic at levels far exceeding those normally prescribed.

Culbert cites a study in Ohio showing toxicity in test animals when up to 1.3 grams per kilogram of body weight were given to monkeys and 6.4 grams per kilogram of body weight given to dogs. Extrapolated to humans, these are levels from five to 300 times the normal oral dose.

He also criticizes a an often-quoted study at University of California Davis in 1978 demonstrating that consumption of certain vegetables with along with oral laetrile could be lethal, and that the often-recommended "laetrile diet" was dangerous. The dogs, he says, were starved, drugged to prevent vomiting, and fed (via a gastric tube) a mash of sweet almonds with amygdalin at a temperature that allowed enzymes in the almonds to "hydrolyze" the amygdalin, causing cyanide release and toxicity in several dogs. Culbert argues the methodology of this and other toxicity tests had little to do with the way patients consume laetrile.

Laetrile opponents also have pointed to the prevalence of impure and potentially dangerous laetrile products, as well as those sold as laetrile which were in fact not laetrile at all. But Culbert and others have countered that these were the outcome of a situation where existing demand was being met by unscrupulous vendors because legal avenues of obtaining the pure product were closed.

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...

Notable 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.

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.

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 life-and-death decisions between a physician and a patient, particularly when the patient is said to be "terminal," as with cancer?

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.

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