Table of Contents
Levels Of Evidence
Glossary Of Terms
For More Information
This complementary and
alternative medicine (CAM) information summary is 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. A glossary of scientific
terms used in the summary appears just before the references. Terms defined
in the glossary are marked in the text by hypertext links.
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 1-5] 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 2,6,7] 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.[8, reviewed in 9]
In the United States, researchers must file an Investigational New Drug
(IND) application with the Food and Drug Administration (FDA) to conduct
clinical 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 3,10,11] and because there were
questions about how the proposed study was to be conducted.[reviewed in 12]
Laetrile supporters viewed this reversal as an attempt by the U.S. 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
U.S. Supreme Court overturned decisions by the lower courts, thereby
re-affirming the FDA's position that drugs must be proven to be both safe and
effective before widespread public use.[reviewed in 2,13] As a result, the
use of laetrile as a cancer therapy is not approved in the United States, but
it continues to be manufactured and administered as an anticancer treatment,
primarily in Mexico.
Although the names laetrile, LaetrileŽ, and amygdalin are often used
interchangeably, they are not the same product. The chemical composition of
U.S. patented LaetrileŽ (mandelonitrile-beta-glucuronide), a semi-synthetic
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 14,15] Mandelonitrile,
which contains cyanide, is a structural component of both products.[reviewed
in 14] It has been proposed that cyanide is the active cancer-killing
ingredient in laetrile, but two other breakdown products of amygdalin,
prunasin (which is similar in structure to LaetrileŽ) and
benzaldehyde, may also be cancer cell
inhibitors.[16,17,18,19] 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 here; 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
therapy. The incidence of cyanide poisoning is much higher when laetrile
is taken orally [20, reviewed in 21,22] 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 16,21]
Relatively little breakdown to yield cyanide occurs when laetrile is
injected.[reviewed in 6,21] Administration schedules and the length of
treatment in animal models and humans vary
Amygdalin was first isolated in 1830 by two French chemists.[reviewed in
3,22] It was used as an anticancer agent in Russia as early as 1845, with
positive results reported for the first patient treated.[reviewed in 5] Its
first recorded use in the United States as a treatment for cancer occurred in
the early 1920s.[reviewed in 2] 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
LaetrileŽ.[reviewed in 3,14,15]
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
section), cyanide is believed to be the active cancer-killing ingredient in
laetrile.[16,17] 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 3,9,15,16,23] Cyanide can also be produced from
prunasin, which is a less-than-complete breakdown product of
amygdalin.[reviewed in 3,16]
Four different theories have been advanced to explain the anticancer
activity of laetrile. The first of these incorporates elements of the
trophoblastic theory of malignancy, 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, give rise to eggs or sperm), some of which become dispersed
throughout the body during embryonic development and are not confined to the
testes and 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.[24, reviewed in 25-29] 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 the modified compound down,
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 two enzymes.[reviewed in 9,25,30,31,32] 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.[33,34]
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 2,3,21,25,27,30,35] Evidence from
laboratory studies demonstrates that this theory cannot be supported. As
noted previously, normal cells and cancer cells contain similar amounts of
rhodanese. Furthermore, most types of mammalian cells contain only small
traces of beta-glucosidase, and this enzyme has not
been detected in tumor samples [16,36] or in human blood. 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 6,30,37,38]
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 39,40]
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 27] According to this
theory, another consequence of lysosome disruption is
stimulation of the immune system.
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,[20,41-51] dogs,[10,52
reviewed in 3] rabbits,[reviewed in 3] and a cat. 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.[20, reviewed in 3] In two 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.[41,42] 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). Amygdalin at every dose
level tested produced no response either as a single
agent or in combination with beta-glucosidase. However, it was discovered
that animals experienced more side effects when beta-glucosidase was given
concurrently (at the same time) with amygdalin than with amygdalin
Additional cell culture and animal studies involving more than a dozen
other tumor models have been published.[20,28,36,43,44,46,47,49,50,53-55] 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. However, positive results were obtained in four
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. 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
In the second study, white blood cells and
prostate cancer specimens were used to investigate the potential of amygdalin
to stimulate the immune system. 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
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. 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 amygdalin down 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
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. 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 two 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 two 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
co-culture 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 co-culture 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,
intramuscular injection.[20,45,52,56, reviewed in
16,31,48,49] As noted previously (History section), most
mammalian cells contain only trace amounts of the enzyme
beta-glucosidase; however, this enzyme is present in
gastrointestinal tract bacteria and in
many food plants.[reviewed in 3,21,23,30,45,48] Two studies have specifically
examined the role of intestinal bacteria in the
breakdown of orally administered amygdalin.[38,48] 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. 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
intramuscularly delivered amygdalin occurs in
humans, with most of the intact compound eventually excreted in
Laetrile has been used as an anticancer treatment in humans
worldwide.[reviewed in 10] Although many
anecdotal reports and
case reports are available, findings from only two
clinical trials [8,56] 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.[26,9,31,32,58,reviewed in 10]
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, 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 LaetrileŽ (total dose range, 9 to 133
grams). 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
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. 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.[18,19]
In one series, 19 complete responses and 10
partial responses were reported among 57
patients who had received either oral or
benzaldehyde; however, precise
response durations were specified for only two of the
patients. Another series by the same investigators used 4,6-benzylidene-
alpha-D-glucose, which is an intravenous
formulation of benzaldehyde. 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 NCI requested case reports from
practitioners who believed their patients had benefited from laetrile
treatment. 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 others had
partial responses while using laetrile. 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. 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. The majority of
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
one month before treatment with amygdalin. Amygdalin, evaluated for potency
and purity by the NCI, was administered
intravenously for 21 days, followed by
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
patients had measurable disease progression at the
end of the intravenous course of treatment, and all
patients had progression seven 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.
On the basis of this phase II study, NCI concluded that no further
investigation of laetrile was warranted. However, several concerns have
been expressed about the study.[reviewed in 5]
Variations in commercial preparations of laetrile from Mexico, the primary
supplier, have been documented.[60,62] Incorrect product labels have been
found, and samples contaminated with bacteria and other substances have been
identified.[60,62] 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.
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,[8, reviewed in
15] cyanosis (bluish discoloration of the skin due to
oxygen-deprived hemoglobin in the blood), liver damage,[63,64]
hypotension (abnormally low blood
pressure),[31,reviewed in 1,3] ptosis (droopy upper
neuropathies (difficulty walking due to damaged
nerves), fever,[65, reviewed in 3] mental confusion, coma, and
death.[reviewed in 23,31,56] 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),[20,52,64,reviewed in 15,21] or
taking high doses of vitamin C.[64,68,reviewed in 1]
Levels of Evidence for Human Studies of Cancer
Complementary and Alternative Medicine
To assist readers in evaluating the results of human studies of 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 levels of evidence analysis, a study must 1) be
published in a peer-reviewed, scientific journal; 2) report on a therapeutic
outcome(s), such as tumor response, improvement in survival, or measured
improvement in quality of life; and 3) 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, please click
on the following link:
Levels of Evidence
Analysis for Human Studies of Cancer Complementary and Alternative
Laetrile/Amygdalin Summary: Reference
Numbers and the Corresponding Levels of Evidence
Strength of Study Design
Strength of Endpoints Measured
||3iii Nonconsecutive Case Series
||Diii Indirect Surrogates -- Tumor Response Rate
||3iii Nonconsecutive Case Series
||Diii Indirect Surrogates -- Tumor Response Rate
||3iii Nonconsecutive Case Series
||Diii Indirect Surrogates -- Tumor Response Rate
||4 Best Case Series
||Diii Indirect Surrogates -- Tumor Response Rate
||4 Best Case Series
||Diii Indirect Surrogates -- Tumor Response Rate
||4 Best Case Series
||Diii Indirect Surrogates -- Tumor Response Rate
||3iii Nonconsecutive Case Series
||Diii Indirect Surrogates -- Tumor Response Rate
Glossary of Terms
adenocarcinoma: Cancer that begins in cells that line certain
internal organs and that have glandular (secretory) properties.
adenopathy: Large or swollen lymph glands.
report: 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.
model: 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.
antibiotic: A drug used to treat infections caused by
bacteria and other microorganisms.
A type of protein produced by certain white blood cells in response to a
foreign substance (antigen). Each antibody can bind to only a 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 disable antigens directly. Others make the antigen more
vulnerable to destruction by white blood cells.
Loss of muscle coordination.
benzaldehyde: A colorless oily liquid used as a flavoring
agent and to make dyes, perfumes, and pharmaceuticals. Benzaldehyde is
chemically related to benzene.
carcinosarcoma: 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).
report: 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).
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.
chemotherapy: Treatment with anticancer drugs.
series: A case series in which the patients receive treatment in a
clinic or other medical facility.
clinical trial: A research study that evaluates the effectiveness of
new interventions in people. Each study is designed to evaluate new methods
of screening, prevention, diagnosis, or treatment of a disease.
and alternative medicine: CAM. Forms of treatment in addition to
(complementary) or instead of (alternative) standard treatments. These
practices include dietary supplements, megadose vitamins, herbal preparations,
special teas, massage therapy, magnet therapy, spiritual healing, and
response: The disappearance of all signs of cancer. Also called a
concurrent therapy: A treatment that is given at the same
time as another.
controlled clinical trial: A clinical study that includes a
comparison (control) group. The comparison group receives a placebo, another
treatment, or no treatment at all.
cell line: Cells of a single type that have been grown in the
laboratory for several generations (cell divisions).
cells: Animal or human cells that are grown in the laboratory.
cyanogenic glucoside: A plant compound that contains sugar
and produces cyanide.
Blue colored skin caused by too little oxygen in the blood.
derivative: In chemistry, a compound produced from or related
diagnosis: The process of identifying a disease by the signs
protein that speeds up the rate at which chemical reactions take place in the
evaluable patients: Patients whose response to a treatment
can be measured because enough information has been collected.
radicals: Highly reactive chemicals that often contain oxygen and are
produced when molecules are split to give products that have unpaired
electrons. This process is called oxidation. Free radicals can damage
important cellular molecules such as DNA or lipids or other parts of the cell.
irradiation: A type of radiation therapy that uses gamma radiation.
Gamma radiation is a type of high-energy radiation that is different from
gastric: Having to do with the stomach.
gastrointestinal tract: The stomach and intestines.
germ-free: Free of bacteria, disease-causing viruses, and
other organisms that can cause infection.
glycoprotein: A protein that has sugar molecules attached to
hydrolysis: A chemical reaction that uses water to break down
hypotension: Abnormally low blood pressure.
Having too little oxygen.
intestinal: Relating to the intestines.
intestine: A long, tube-shaped organ in the abdomen that
completes the process of digestion. People have a large intestine and a small
intestine. Also called the bowel.
intracellular: Inside a cell.
intramuscular: IM. Within or into muscle.
intraperitoneal: IP. Within the peritoneal cavity (the area
that contains the abdominal organs).
intravenous: IV. Into a vein.
lymph node: A rounded mass of lymphatic tissue that is surrounded by
a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are
spread out along lymphatic vessels and they contain many lymphocytes, which
filter the lymphatic fluid (lymph).
A sac-like compartment inside a cell that has enzymes that can break down
cellular components that need to be destroyed.
maintenance therapy: Treatment that is given to help extend
the benefit of previous therapy. Maintenance therapy is often given to reduce
the risk of relapse in persons whose cancer is in remission.
metabolic: Having to do with metabolism.
metabolic disorder: A condition in which normal metabolic
processes are disrupted, usually because of a missing enzyme.
therapy: Treatment to correct changes in metabolism that can be
caused by disease.
metabolism: The total of all chemical changes that take place
in a cell or an organism. These changes produce energy and basic materials
that are needed for important life processes.
metastatic: Having to do with metastasis.
metastasis: The spread of cancer from one part of the body to
another. Tumors formed from cells that have spread are called "secondary
tumors," and contain cells that are like those in the original (primary)
tumor. The plural is metastases.
A chemical made up of two or more atoms. The atoms in a molecule 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.
nasal: By or having to do with the nose.
neuropathy: A problem in any part of the nervous system
except the brain and spinal cord. Neuropathies can be caused by infection,
toxic substances, or disease.
neurotoxin: A substance that is poisonous to nerve tissue.
objective response: A measurable response.
oral: By or
having to do with the mouth.
A living entity, such as an animal, a plant, a bacterium, or a fungus.
osteogenic sarcoma: A malignant tumor of the bone. Also
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
pancreatic: Having to do with the pancreas.
pancreatic enzymes: A group of proteins secreted by the
pancreas which aid in the digestion of food.
partial response: The shrinking, but not complete
disappearance, of a tumor in response to therapy. Also called partial
trial: Phase I trials are 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 drug is usually given in progressively higher doses to determine the
highest dose that does not cause harmful side effects. Because little is
known about the possible risks and benefits of treatments being tested, phase
I trials usually include only a limited number of patients who have not been
helped by other known treatments.
trial: Phase II trials focus on learning whether the new treatment
has an anticancer effect (for example, whether it shrinks a tumor, or improves
blood test results), and whether it is effective for a particular type of
tumor: The original tumor.
progression: An increase in scope or severity of a disease.
Drooping of the upper eyelid.
therapy: The use of high-energy radiation from x-rays, neutrons, and
other sources to kill cancer cells and shrink tumors. Radiation may come from
a machine outside the body (external-beam radiation therapy) or from materials
(radioisotopes) that produce radiation that are placed in or near a tumor or
in the area where cancer cells are found (internal radiation therapy, implant
radiation, or brachytherapy). Systemic radiation therapy involves giving a
radioactive substance, such as a radiolabeled monoclonal antibody, that
circulates throughout the body. Also called radiotherapy.
rectal: By or having to do with the rectum, which is the last 8 to
10 inches of the large intestine ending at the anus.
In oncology, describes the body area right around a tumor.
regression: A decrease in the extent or size of cancer.
In medicine, an improvement related to treatment.
symptomatic: Having to do with the symptoms of disease or its
Affecting the entire body.
Having to do with urine or the organs of the body that produce and get rid of
cell: Refers to cells in the immune system that help the body fight
infection and disease. White blood cells include lymphocytes, granulocytes,
macrophages, and others.
xenograft: The cells of one species transplanted to another
1. Howard-Ruben J, Miller NJ: Unproven methods
of cancer management part II: current trends and implications for patient
care. Oncology Nursing Forum 11(1): 67-73, 1984.
2. Curt GA: Unsound methods of cancer treatment. Principles & Practice of
Oncology Updates 4(12): 1-10, 1990
3. Dorr RT, Paxinos J: The current status of laetrile. Annals of Internal
Medicine 89(3): 389-397, 1978.
4. Calabrese EJ: Possible adverse side effects from treatment with
laetrile. Medical Hypotheses 5(9): 1045-1049, 1979.
5. Moss RW: The Cancer Industry: The Classic Exposé on the Cancer
Establishment. Brooklyn, NY: First Equinox Press, 1996. pp. 131-185.
6. Lerner IJ: Laetrile: a lesson in cancer quackery. CA-A Cancer Journal
for Clinicians 31(2): 91-95, 1981.
7. Ellison NM, Byar DP, Newell GR: Special report on laetrile: the NCI
laetrile review: results of the National Cancer Institute's retrospective
laetrile analysis. New England Journal of Medicine 299(10): 549-552, 1978.
8. Moertel CG, Fleming TR, Rubin J, et al.: A clinical trial of amygdalin
(laetrile) in the treatment of human cancer. New England Journal of Medicine
306(4): 201-206, 1982.
9. Ross WE: Unconventional cancer therapy. Comprehensive Therapy 11(9):
10. Lewis JP: Laetrile. Western Journal of Medicine 127(1): 55-62, 1977.
11. American Cancer Society: Unproven methods of cancer management:
laetrile. CA-A Cancer Journal for Clinicians 22(4): 245-250, 1972.
12. Rosen GM, Shorr RI: Laetrile: end play around the FDA: a review of
legal developments. Annals of Internal Medicine 90(3): 418-423, 1979.
13. Curran WJ: Laetrile for the terminally ill: Supreme Court stops the
nonsense. New England Journal of Medicine 302(11): 619-621, 1980.
14. Fenselau C, Pallante S, Batzinger RP, et al.: Mandelonitrile
beta-glucuronide: synthesis and characterization. Science 198(4317): 625-627,
15. Chandler RF, Anderson LA, Phillipson JD: Laetrile in perspective.
Canadian Pharmaceutical Journal 117(11): 517-520, 1984.
16. Newmark J, Brady RO, Grimley PM, et al.: Amygdalin (laetrile) and
prunasin beta-glucosidases: distribution in germ-free rat and in human tumor
tissue. Proceedings of the National Academy of Sciences USA 78(10): 6513-
17. Rauws AG, Olling M, Timmerman A: The pharmacokinetics of prunasin, a
metabolite of amygdalin. Journal of Toxicology: Clinical Toxicology 19(8):
18. Kochi M, Takeuchi S, Mizutani T, et al.: Antitumor activity of
benzaldehyde. Cancer Treatment Reports 64(1):21-23, 1980.
19. Kochi M, Isono N, Niwayama M, et al.: Antitumor activity of a
benzaldehyde derivative. Cancer Treatment Reports 69(5): 533-537, 1985.
20. Gostomski FE: The effects of amygdalin of the Krebs-2 carcinoma and
adult and fetal DUB(ICR) mice. Dissertation Abstracts International B 39(5):
21. Herbert V: Laetrile: the cult of cyanide. Pomoting poison for profit.
American Journal of Clinical Nutrition 32(5): 1121-1158, 1979.
22. Viehoever A, Mack H: Bio-chemistry of amygdalin. The American Journal
of Pharmacy 107: 397-450, 1935.
23. Ames MM, Moyer TP, Kovach JS, et al.: Pharmacology of amygdalin
(laetrile) in cancer patients. Cancer Chemotherapy and Pharmacology 6(1): 51-
24. Krebs ET Jr, Krebs ET Sr, Beard HH: The unitarian or trophoblastic
thesis of cancer. Medical Record 163(7): 149-174, 1950.
25. Ellison NM: Unproven methods of cancer therapy. Drug Therapy 10: 73-
26. Navarro MD: The Philippine experience in the early detection and
chemotherapy of cancer. Santo Tomas Journal of Medicine 25(3): 125-133, 1970.
27. Greenberg DM: The case against laetrile: the fraudulent cancer remedy.
Cancer 45(4): 799-807, 1980.
28. Levi L, French WN, Bickis IJ, et al.: Laetrile: a study of its
physicochemical and biochemical properties. Journal of the Canadian Medical
Association, 92: 1057-1061, 1965.
29. Report by the Cancer Commission of the California Medical Association:
The treatment of cancer with "laetriles". California Medicine 78(4): 320-326,
30. American Cancer Society: Unproven methods of cancer management:
laetrile. CA-A Cancer Journal for Clinicians 41(3): 187-192, 1991.
31. Navarro MD: Five years experience with laetrile therapy in advanced
cancer. Acta Unio Internationalis Contra Cancrum 15(suppl 1): 209-221, 1959.
32. Morrone JA: Chemotherapy of inoperable cancer: preliminary report of
10 cases treated with laetrile. Journal of Experimental Medicine and Surgery
20: 299-308, 1962.
33. 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 Research 12: 574-579, 1952.
34. Conchie J, Findlay J, Levvy GA: Mammalian glycosidases: distribution
in the body. Biochemistry 71: 318-325, 1959.
35. Scott PJ: Laetrile and cancer quackery problems. Cancer Forum 5(2):
36. Biaglow JE, Durand RE: The enhanced radiation response of an in vitro
tumour model by cyanide released from hydrolysed amygdalin. International
Journal of Radiation Biology 33(4): 397-401, 1978.
37. Lerner IJ: The whys of cancer quackery. Cancer 53(suppl 3): 815-819,
38. Shils ME, Hermann MG: Unproved dietary claims in the treatment of
patients with cancer. Bulletin of the New York Academy of Medicine 58(3):
39. Young VR, Newberne PM: Vitamins and cancer prevention: issues and
dilemmas. Cancer 47(suppl 5): 1226-1240, 1981.
40. Jukes TH: Laetrile struggles. Nature 263(5578): 543, 1976.
41. 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 Chemotherapy Reports 59(5):
42. 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 Chemotherapy Reports 59(5): 951-965,
43. Stock CC, Tarnowski GS, Schmid FA, et al.: Antitumor tests of
amygdalin in transplantable animal tumor systems. Journal of Surgical
Oncology 10(2): 81-88, 1978.
44. Menon MM, Bhide SV. Perinatal carcinogenicity of isoniazid (INH) in
Swiss mice. Journal of Cancer Research and Clinical Oncology 105(3):258-261,
45. Newton GW, Schmidt ES, Lewis JP, et al.: Amygdalin toxicity studies in
rats predict chronic cyanide poisoning in humans. Western Journal of Medicine
134(2): 97-103, 1981.
46. Hill GJ II, Shine TE, Hill HZ, et al.: Failure of amygdalin to arrest
B16 melanoma and BW5147 AKR leukemia. Cancer Research 36(6): 2102-2107, 1976.
47. Lea MA, Koch MR: Effects of cyanate, thiocyanate, and amygdalin on
metabolite uptake in normal and neoplastic tissues of the rat. Journal of the
National Cancer Institute 63(5): 1279-1283, 1979.
48. Carter JH, McLafferty MA, Goldman P: Role of the gastrointestinal
microflora in amygdalin (laetrile)-induced cyanide toxicity. Biochemical
Pharmacology 29(3): 301-304, 1980.
49. Khandekar JD, Edelman H: Studies of amygdalin (laetrile) toxicity in
rodents. Journal of the American Medical Association 242(2): 169-171, 1979.
50. Manner HW, DiSanti SJ, Maggio MI, et al.: Amygdalin, vitamin A and
enzyme induced regression of murine mammary adenocarcinomas. Journal of
Manipulative and Physiological Therapeutics 1(4): 246-248, 1978.
51. Ovejera AA, Houchens DP, Barker AD, et al.: Inactivity of DL-amygdalin
against human breast and colon tumor xenografts in athymic (nude) mice.
Cancer Treatment Reports 62(4): 576-578, 1978.
52. Schmidt ES, Newton GW, Sanders SM, et al.: Laetrile toxicity studies
in dogs. Journal of the American Medical Association 239(10): 943-947, 1978.
53. Bhatti RA, Ablin RJ, Guinan PD: Tumour-associated directed immunity in
prostatic cancer: effect of amygdalin. IRCS Medical Science 9(1): 19, 1981.
54. Koeffler HP, Lowe L, Golde DW: Amygdalin (laetrile): effect on
clonogenic cells from human myeloid leukemia cell lines and normal human
marrow. Cancer Treatment Reports 64(1): 105-109, 1980.
55. 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. International Journal of
Cancer 78(6): 712-719, 1998.
56. Moertel CG, Ames MM, Kovach JS, et al.: A pharmacologic and
toxicological study of amygdalin. Journal of the American Medical Association
245(6): 591-594, 1981.
57. Ames MM, Kovach JS, Flora KP: Initial pharmacologic studies of
amygdalin (laetrile) in man. Research Communications in Chemical Pathology
and Pharmacology 22(1): 175-185, 1978.
58. Brown WE, Wood CD, Smith AN: Sodium cyanide as a cancer
chemotherapeutic agent: laboratory and clinical studies. American Journal of
Obstetrics and Gynecology 80(5): 907-918, 1960.
59. Newell GR, Ellison NM: Ethics and designs: laetrile trials as an
example. Cancer Treatment Reports 64(2-3): 363-365, 1980
60. Davignon JP, Trissel LA, Kleinman LM: Pharmaceutical assessment of
amygdalin (laetrile) products. Cancer Treatment Reports 62(1): 99-104, 1978.
61. Sun M: Laetrile brush fire is out, scientists hope. Science
212(4496): 758-759, 1981.
62. Davignon JP: Contaminated laetrile: a health hazard. New England
Journal of Medicine 297(24): 1355-1356, 1977.
63. Leor R, Michaeli J, Brezis M, et al.: Laetrile intoxication and
hepatic necrosis: a possible association. Southern Medical Journal 79(2):
64. Lee M, Berger HW, Givre HL, et al.: Near fatal laetrile intoxication:
complete recovery with supportive treatment. Mount Sinai Journal of Medicine
49(4): 305-307, 1982.
65. Smith FP, Butler TP, Cohan S, et al.: Laetrile toxicity: a report of
two patients. Cancer Treatment Reports 62(1): 169-171, 1978.
66. Vizel M, Oster MW: Ocular side effects of cancer chemotherapy. Cancer
67. Kalyanaraman UP, Kalyanaraman K, Cullinan SA, et al.: Neuromyopathy of
cyanide intoxication due to "laetrile" (amygdalin). Cancer 51(11): 2126-2133,
68.Calabrese EJ: Conjoint use of laetrile and megadoses of ascorbic acid in
cancer treatment: possible side effects. Medical Hypotheses 5(9): 995-997,
For More Information
For more information on complementary and alternative therapies, contact
the NIH National Center for Complementary and Alternative Medicine (NCCAM):
- NCCAM Clearinghouse
Post Office Box 8218
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TTY/TDY: 1-888-644-6226 (toll free)