What are some of the best treatments that
can be used by naturopathic doctors for the treatment of cancer?
There are dozens, but in this
article, I will discuss a number of the most promising: Avemar, cimetidine,
maitake, melatonin, pau d'arco, and Sun soup.
Sold in the US under the brand name Avé, Avemar is a nutritional supplement
manufactured from fermented wheat germ. Avemar helps regulate the processes
of cellular metabolism and supports mechanisms of immune regulation. The active
ingredients of Avemar are several ubiquinones – in particular, DMBQ (standardized
2-methoxy benzoquinone and 2,6 dimethoxybenzoquinone). There have been some
formal clinical and laboratory investigations of Avemar, and the picture that
emerges is a highly positive one. For instance, a study published in the Journal
of Pediatric Hematology and Oncology found that fermented wheat germ could
reduce chemotherapy-induced neutropenia in children undergoing treatment for
various kinds of leukemia (Garami 2004).
Avemar also has supportive value in colorectal cancer (Jakab 2003). A Hungarian
clinical trial showed that Avemar, when added to standard therapy for stage
III colorectal cancer, had important adjunctive effects: 170 colorectal cancer
patients received standard anticancer therapies. Of this group, 66 also received
this fermented wheat germ extract. The new recurrence rate was just three percent
in the Avemar group vs. 17.3% in the standard group. Similarly, the death rate
was just 12.1% vs. 31.7% in the standard treatment group (Farkas 2005).
Cimetidine (Tagamet) is a readily available, over-the-counter ulcer and indigestion
remedy that has demonstrated some surprising anticancer effects. Roswell
Park Cancer Institute (Buffalo, New York) scientists have shown cimetidine
to be a "potent immunomodulating agent" (Nakajima 1991) that
reverses the decline in the cellular-mediated immunity often seen in cancer
patients (Nishiguchi 2003).
The first positive report on cimetidine came from Dr. James O. Armitage, MD,
past president of the American Society of Clinical Oncology (ASCO), at the
University of Nebraska, Omaha. He gave cimetidine to two lung cancer patients,
one of whom had brain metastases. Both patients experienced unanticipated remissions
of their cancer (Armitage 1979). In 1982, late-stage cancer patients were given
1,000 mg per day of cimetidine for gastric distress. Several had rapid remissions
of their cancer. Other late-stage cancer patients also had impressive remissions
(Thornes 1982; Borgstrom 1982).
Cimetidine has also been shown to potentiate interferon therapy in advanced
melanoma. Dr. Per Flodgren reported that while no objective tumor responses
were recorded with interferon treatment alone, six patients had objective tumor
regressions when cimetidine was added to their interferon treatment (Flodgren
1983 and 1985).
At the 1999 ASCO meeting, Japanese scientists reported on the use of cimetidine
in stomach cancer. Sixteen patients with progressive gastric cancer with distant
metastases, and nine patients whose gastric cancer had recurred after surgery
underwent chemotherapy plus cimetidine. A complete response of metastatic lesions
was found in five cases and a partial response in 16 cases. Although the number
of cases was rather small, the combination was effective in 21 out of 25, or
84% (Watanabe 1999).
At the 2004 ASCO meeting, Japanese scientists reported on a randomized clinical
trial in patients with advanced renal cell carcinoma with lung metastases.
Seventy-one patients from 32 institutions were randomly assigned to get either
interferon-alfa (IFN) or IFN plus cimetidine. Among 36 evaluable patients in
the IFN-alone group, there was a response rate of 15.2 %. But of 35 patients
in IFN-plus-cimetidine group, there was a response rate of 29.4 % (Kinouchi
The usual dose of cimetidine for indigestion is 200 milligrams per day; however,
in cancer, the effective dose seems to be between 800 and 1,000 mg per day.
Even so, the cost is low. Patients should take this only under a doctor's
supervision since cimetidine, albeit over-the-counter in the US, is a powerful
drug that can occasionally interact with other drugs. The most dangerous potential
interaction is with the anticancer agent BCNU (BiCNU or carmustine), used primarily
for brain cancer. It has been known for decades that cimetidine can increase
BCNU's bone marrow toxicity and that this interaction could be life-threatening
(Selker 1978). There are also potential interactions with the drugs warfarin
(Coumadin) and theophylline, an ingredient in tea and coffee.
A useful Asian medicinal mushroom is Grifola frondosa, known in Japanese as
maitake. There are 25 articles on maitake and cancer listed in PubMed, most
from the laboratory of Hiroaki Nanba, PhD, of Kobe Pharmaceutical University,
Japan. Dr. Nanba isolated the D-fraction beta-glucan from maitake. Maitake
D-Fraction has been found to enhance both arms of the immune response in
normal mice. Therefore, Nanba concludes, "its administration may enhance
host defense against foreign pathogens and protect healthy individuals from
infectious diseases" (Kodama 2004). In some experiments, maitake D-Fraction
also appears to arrest the progression of cancer cells. It primarily exerts
this effect through stimulation of natural killer (NK) cell activity (Kodama
2003). It appears to work well with chemotherapy (Nie 2006).
In one of the most positive experiments, metastases to the liver were reduced
by 81.3% in mice taking the oral maitake and 91.3% in the mice given injections
of the D-fraction. Cancer cells present in the blood and/or lymph were killed
via immune mechanisms that had been activated by the mushroom (Nanba 1995).
D-fraction has the added benefit that it can be delivered as drops placed under
the tongue. It is thus suitable for patients whose advanced disease prevents
them from eating solid foods or supplements, such as those patients with cachexia
Melatonin, the main hormone responsible for regulating sleep, was first isolated
and characterized in 1958. Although known primarily as a regulator of circadian
rhythms, melatonin has also been shown to exert anticancer activity through
five different mechanisms. These are: 1) an anti-proliferative effect on
cancer cells; 2) stimulation of anticancer immunity; 3) changes in the expression
of oncogenes; 4) its role as a powerful antioxidant; and 5) anti-angiogenic
There are over 1,000 PubMed-listed articles on the topic of melatonin and
cancer, of which 66 are clinical trials. Dr. Paolo Lissoni, of Monza, Italy,
that under experimental conditions, a neuroendocrine disorder precedes the
development of clinical cancer. Every condition that diminishes the healthy
functioning of the pineal gland and its output of melatonin, he says, increases
the risk of cancer. When asked about causes of this malfunction of the "master
gland," and therefore of cancer itself, Dr. Lissoni has singled out electromagnetic
field emissions, chronic emotional stress, and mental depression. Such malfunctions,
he says, almost always have significance in regard to the development of cancer.
In 1992, Dr. Lissoni's group found that adding melatonin to chemotherapy
in metastatic non-small cell lung cancer (NSCLC) treatment had a beneficial
effect on survival. All the patients in question had declined after receiving
first-line chemotherapy containing cisplatin. The study included 63 patients
who were randomized to receive either melatonin or best supportive care (BSC)
alone. Patients were given ten milligrams per day of melatonin. These patients
were then followed for one year from the time of progression after chemotherapy
and were compared to the control group, which was randomized to receive supportive
care alone. The percentage of both stabilization of disease and survival at
one year was significantly higher in patients treated with melatonin than in
those treated only with supportive care. In addition, not only was no drug-related
toxicity noted but, on the contrary, treated patients "showed a significant
improvement in performance status."
Two years later, Lissoni's group published an article in which they showed
that melatonin added to the standard immune stimulant interleukin 2 (IL-2)
increased survival, even in cancers in which IL-2 was not conventionally thought
to be effective. This study was carried out in patients who had either locally
advanced or metastatic solid tumors. The study included 80 consecutive patients,
who were randomized to receive either IL-2 alone subcutaneously or IL-2 plus
40 mg per day of melatonin.
A complete response was obtained in none of the patients receiving IL-2 alone
but in three of the 41 patients treated with IL-2 plus melatonin. A partial
response was achieved in only one out of 39 patients treated with IL-2 alone
but in eight of the 41 patients treated with IL-2 plus melatonin. Thus, the
overall objective response rate was ten times greater (26.8%) in the melatonin-added
group than in the group that received just IL-2. Not surprisingly, this difference
was statistically significant (Lissoni 1994).
Pau d'arco is an ancient South American folk remedy, derived from the
inner bark of a trumpet-flowered cross vine, Tabebuia impetiginosa (Argentina)
or Tabebuia heptaphylla (Brazil). These are both members of the Bignonia family,
plants that are native to the Caribbean and Central and South America, but
that are now grown in the southern US as well.
Pau d'arco is one folk remedy that seems to also have a rational basis.
There are at least twelve aromatic compounds in pau d'arco, the best-known
and studied of which is lapachol, which was isolated in the 1850s from the
wood of a Brazilian tree. In the 1960s, this was found to inhibit the growth
of the Walker 256 rat carcinoma cell line when given orally (Rao 1968).
As a result of this study, Jerome Block, MD, performed a clinical trial in
which 19 patients with advanced nonleukemic tumors and two with chronic myelocytic
leukemia in relapse were given lapachol, in doses ranging from 250 to 3,750
milligrams per day. All 21 patients had previously and unsuccessfully received
a variety of other therapies. One patient with metastatic breast cancer was
cured of a single hip tumor, but there was no change in her numerous other
bony lesions. All other patients either remained clinically unimproved or experienced
advancing disease. But this trial may have been too short in duration to show
pau d'arco's true effects. Pau d'arco may well be beneficial
to cancer patients when taken over a period of months. There is, to my knowledge,
minimal toxicity when taken as directed on the package. Pau d'arco is
inexpensive and widely available in most countries. Unfortunately, the potency
and authenticity of most pau d'arco remains murky, as there is no organization
that independently assays medicinal herbs for purity, potency, safety, or efficacy.
(Consumerlab.com has never, to my knowledge, done a review.) The safest bet
would be to buy a reputable national brand.
This dietary-herbal supplement is centered around shiitake mushrooms and contains
other mushrooms, soy, and Asian herbs. Alexander S. Sun, PhD, was a biochemist
from the University of California, Berkeley, who did research at Mt. Sinai
Medical Center, New York, and Yale University. He also directed an independent
research laboratory in Milford, Conn. (Dr. Sun died of a sudden heart attack
in July 2006.)
In 1984, Sun's mother developed lung cancer, which had metastasized to
the lymph nodes and adrenal glands. She had surgery and a form of chemotherapy,
but because of the severity of her case, survival seemed most unlikely. Dr.
Sun therefore searched out Chinese food substances that had been demonstrated
in the laboratory to have anticancer effects. From this information, he devised
an immune-stimulating "soup" for his mother. Within eight months,
her lung cancer was in complete remission. Many years later, she was alive,
well, and free of cancer.
Dr. Sun then began making the soup for others – at first for friends,
then commercially. Anecdotally, some patients reported good results. It was
also studied clinically in patients with advanced non-small cell lung cancer.
Today, both frozen and freeze-dried soups are marketed in the US as dietary
supplements. Daily doses were used in the clinical studies in patients with
advanced non-small cell lung cancer.
The soup was tested in standard Balb/C mice and produced between 53% and 74%
inhibition of tumor growth; one out of eight animals had a complete tumor regression
(CAP-CAM 1999). The first clinical paper concerned stage IIB and IV non-small
cell lung cancer patients treated with this vegetable product and conventional
therapies. Sun's coworker, Dr. Tom M. Fasy, reported on 14 out of 18
patients who took the soup for two months or more. These patients lived longer
than patients who received chemotherapy alone (Sun 2001).
A controlled trial was also undertaken at the University of Palacky, Czech
Republic. The control group consisted of 13 stage III and IV advanced lung
cancer patients who did not eat the soup. The performance status in the comparable
treatment group improved significantly. Median survival in the control group
was just four months vs. 15 months in the Sun soup treatment group. A group
of five early-stage patients was also treated for up to 24 months and, during
that time, none had a recurrence of their tumor (Sun 1999).
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Balassiano IT, de Paulo SA, Silva NH, et al. Demonstration of the lapachol
as a potential drug for reducing cancer metastasis. Oncol Rep.
Block JB, Serpick AA, Miller W, et al. Early clinical studies with
lapachol (NSC-11905). Cancer Chemother Rep 2.
Borgstrom S, von Eyben FE, Flodgren P, et al. Human leukocyte interferon
and cimetidine for metastatic melanoma. N Engl J Med.
CAP-CAM 1999: Reported at the Cancer Advisory Panel for Complementary
and Alternative Medicine: Minutes of the First Meeting. July 8-9, 1999.
Farkas E. Fermented wheat germ extract in the supportive therapy of
colorectal cancer. Orv Hetil. 2005
Flodgren P, Malmstrom P, Axelsson B, et al. Immune functions in melanoma
patients during treatment with interferon [HuIFN-alpha (Le)] alone
or in combination with cimetidine. Anticancer Res. 1985;5:197-204.
Flodgren P, Borgstrom S, Jonsson PE, et al. Metastatic malignant melanoma:
regression induced by combined treatment with interferon [HuIFN-alpha(Le)]
and cimetidine. Int J Cancer. 1983;32:657-665.
Garami M, Schuler D, Babosa M, et al. Fermented wheat germ extract
reduces chemotherapy-induced febrile neutropenia in pediatric cancer
patients. J Pediatr Hematol Oncol. 2004,
Jakab F, Shoenfeld Y, Balogh A, et al. A medical nutriment has supportive
value in the treatment of colorectal cancer. Br J Cancer. 2003;89:465-469.
Kinouchi T, Sakamoto J, Tsukamoto T, et al. Prospective randomized
trial of natural interferon-alpha (IFN) versus IFN + cimetidine in
advanced renal cell carcinoma with pulmonary metastasis. Journal
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Grifola frondosa stimulates immune function of normal mice. J
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Lissoni P, Barni S, Ardizzoia A, et al. Randomized study with the pineal
hormone melatonin versus supportive care alone in advanced non-small
cell lung cancer resistant to a first-line chemotherapy containing
cisplatin. Oncology. 1992;49:336-339.
Lissoni P, Barni S, Tancini G, et al. A randomised study with subcutaneous
low-dose interleukin 2 alone vs. interleukin 2 plus the pineal neurohormone
melatonin in advanced solid neoplasms other than renal cancer and melanoma.
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Nakajima I, Chu TM. Synergistic antitumor activity of interleukin-2
and cimetidine against syngeneic murine tumor. Cancer Immunol
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Nie X, Shi B, Ding Y, Tao W. Preparation of a chemically sulfated polysaccharide
derived from Grifola frondosa and its potential biological activities.
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Nishiguchi S, Tamori A, Shiomi S, et al. Cimetidine reduces impairment
of cellular immunity after transcatheter arterial embolization in patients
with hepatocellular carcinoma. Hepatogastroenterology.
Rao K, McBride TJ, Oleson JJ. Recognition and evaluation lapachol as
an antitumor agent. Cancer Res. 1968;28:1952-1954.
Russell WL, Lopez LM. Cimetidine-induced mental status changes: Case
report and literature review. Am J Hosp Pharm. 1980;37:1667-1671.
Selker RG, Moore P, Lodolce D. Bone-marrow depression with cimetidine
plus carmustine. N Engl J Med. 1978;299:834.
Sun AS, Yeh HC, Wang LH, et al. Pilot study of a specific dietary supplement
in tumor- bearing mice and in stage IIIB and IV non-small cell lung
cancer patients. Nutr Cancer. 2001;39:85-95.
Sun AS, Ostadal O, Ryznar V, et al. Phase I/II study of stage III and
IV non-small cell lung cancer patients taking a specific dietary supplement.
Nutr Cancer. 1999;34:62-69.
Thornes RD, Lynch G, Sheehan MV. Cimetidine and coumarin therapy of
melanoma. Lancet. 1982;2:328.
Watanabe S, Izumi S, N Miyosi N, et al. Chemotherapy combined with
cimetidine for recurring and progressive gastric cancer. 1999 ASCO
Annual Meeting Abstract No.1167.