Modified Citrus Pectin
MODIFIED CITRUS PECTIN SLOWS PSA DOUBLING TIME: A
Pilot Clinical Trial
Stephen Strum MD, Mark Scholz MD, Jon McDermed Pharm D, Michael McCulloch BA,
Isaac Eliaz MD
Presented at the International Conference on Diet and Prevention of Cancer
May 28 June 2, 1999
The purpose of this pilot clinical trial was to evaluate the ability of Modified Citrus Pectin
to influence the PSA slope in men with prostate cancer. Patients who had either relapsed
after or failed prior treatment for prostate cancer (PSA range 0.63 to 7.50) were given
Modified Citrus Pectin (PectaSol ®, EcoNugenics, Inc., San Rafael, CA
94901) at a dosage
of 15 grams per day in three divided oral doses. PSA doubling time was calculated. A
response (more than 30% lengthening of PSA doubling time) was seen in 4/7 patients
(57%). One patient (1/7) had a partial response, one patient (1/7) had stable disease, and
one patient (1/7) did not respond. Modified Citrus Pectin appears to lengthen the PSA
doubling time in prostate cancer patients with low levels of PSA. Study responses are
additionally compelling, as all study participants are still alive and evaluable for longterm
followup almost three years after completion of this study. More research involving
larger numbers of patients is needed to full), define the role of MCP in prostate cancer
The purpose of this pilot clinical trial was to evaluate the ability of Modified Citrus Pectin to
influence the PSA slope in men with prostate cancer.
For prostate cancer to spread, research indicates that a clump of cells may be required rather
than a single cell or a few individual cells together. The
ability for cancer cells to "clump" appears to be mediated, at least in part, by
carbohydratebinding, proteins (CBP's) located on the cell surface. One such CBP is a
galactosidebinding lectin or "galectin" called galectin3.
In human studies involving colon, stomach and thyroid cancers, the amounts of galectin produced
increased proportionally as the cancers grew from their earliest to their most advanced stages. It
is reasonable to hypothesize that the higher galectin levels permit greater adhesion and clumping
of cancer cells at a "target site," i.e. the site of metastasis. Thus, these lectin binding
and their ability to bind cell surface carbohydrates and glycoproteins may serve as the cement
that allows cancer cells to clump and possibly bind to metastatic target sites.
Plant fiber derived from citrus fruit contains "citrus pectin", a highly nonbranched
polysaccharide that is rich in galactosyl (sugar carbohydrate) residues. MCP is citrus pectin that
has been pHmodified into smaller, less complex molecules that dissolve much better in water
and are absorbed more completely by the body when taken by mouth. MCP appears to
compete with the galectin3 receptor sites thereby interfering with cancer cellcancer cell
cancer cell-metastatic target site interactions.
In a study by Pienta et al, two groups of rats serving as an animal model for human prostate
cancer were injected with MATLyLu Dunning, R3327 rat prostate adenocarcinorna cells.
(MATLyLu cancer cells grow more rapidly and have a greater tendency to metastasize
throughout the body). Half of the rats were "controls" and were given plain drinking water,
the others were given MCP in their water at a 0.1% concentration.
Results from this study showed 7/14 (50%) of 0.1% MCP-treated rats developed lung,
metastases, which was significantly lower in 15/16 of control animals (93.75%). When 1% MCP
was studied in the same manner, lung metastases occurred in 9/16 (56.3%) of MCPtreated
animals. The number of metastatic colonies in the lungs of the 1.0% MCP group (1 +/- 1) was
significantly lower than in the control group (9 +/- 4).
The same authors later showed that MCP also reduced the ability of rat prostate
adenocareinoma cells to bind to rat endothelial cells (the type of cells that
form the inside lining of blood vessels) in a dosedependent manner. In other words, with higher
doses of MCP, proportionately greater reductions in cancer cell binding to endothelial cells were
observed. When human prostate cancer cells metastasize, they appear to bind to the same target
receptor site, i.e. galectin3, that MCP binds with (Pienta KJ et al, J
Natl Cancer Inst. 87:348-353,1995).
MATERIALS & DOSAGE
Modified Citrus Pectin (PectaSol ®, EcoNugenics, Inc., San Rafael,
CA 94901) was orally
administered at a dosage of 15 grams per clay in three divided doses. The study material
specifications had a molecular weight (MW) of 10,000-15,000 daltons and methylation (DM)
less than 10%.
1) Prostate cancer patients failing firstline androgen deprivation therapy.
2) Patients in relapse after radical prostatectomy, external beam radiation therapy, brachytherapy
3) Untreated patients, or those off Intermittent Hormone Blockade (IHB), both having low levels
of PSA and a defined PSA doubling time.
1) CBC, chemistry panel, PSA and other tumor markers as appropriate.
2) Radiological studies pertinent to the patient's clinical stage of disease.
3) Physical examination and complete review of systems.
All patients were seen in office followups at least once a month. Followup
studies included a CBC, chemistry panel, PSA and/or other tumor markers, physical
examination, and a review of systems. PSA doubling time was plotted using computer software.
The PSA doubling time reflects the speed at which the cancer is growing. The faster the growth,
the shorter the PSA doubling time. Lengthening of the PSA doubling time represents a decrease
in the rate of growth of the cancer. PSA doubling time data was evaluated at 3, 6, and 12
months intervals. A minimum of 3 months on study was required for patients to be evaluable for
CRITERIA FOR STUDY DISCONTINUATION
Patients were discontinued from the study when there was (1) a lack of response to MCP, (2)
clinical findings of progressive disease unrelated to PSA, or (3)
patient intolerance to MCP.
Response = More than 30% lengthening of PSA doubling time
Partial response = Less than 30% lengthening of PSA doubling time
Stable disease = Less than 50% shortening of PSA doubling time
No response = More than 50% shortening in PSA doubling time
Progression = 50% PSA increase above baseline measured on two successive monitoring,
intervals, or clinical evidence for disease progression unrelated to the PSA response.
Clinical Data: MCP Results In 7 Patients With Prostate Cancer
1 DT = PSA Doubling Time
2 Cryo = Cryosurgery
Seven patients were enrolled into this study and considered evaluable. A response (more than
30% lengthening of PSA doubling time) was seen in 4/7 patients (57%). All of these were
patients off IHB. In one patient there was a 5.7% lengthening in his PSA doubling time
(PSADT). He was thus judged to have had a partial response. One patient had a 6.7%
shortening in PSADT. He was judged to have stable disease. The remaining patient had a 69.4%
shortening in PSADT, and so had no response.
Modified Citrus Pectin appears to slow the PSA doubling time in prostate cancer patients with
low levels of PSA. More research involving larger numbers of patients is needed to fully define
the role of MCP in prostate cancer treatment. Study responses are additionally compelling, as all
study participants are still alive and evaluable for longterm followup almost three years after
completion of this study.
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