[MOL] Alt. Med Series [01419] Medicine On Line


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[MOL] Alt. Med Series



 

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SUMMARY OF RESEARCH

No randomized clinical trials have been conducted with cartilage products.

Nine clinical series1,5,6 7-11(one article11reported two series) and one
best case series12 of cartilage have assessed disease response and/or
survival outcomes.

Prudden conducted a clinic series study of patients with a variety of
cancer sites (n=31) who had large tumors with or without metastasis for
whom conventional therapy had failed. Cartilage treatment resulted in 19
patients with complete responses, 10 with partial responses, and 2 with no
response1.

A second clinic series concerned patients with colon, renal, or other
cancers (n=9) with distant non-brain metastases who had received
conventional therapy. This study resulted in one responder (treated for 39
weeks) and eight patients with progressive disease7.

In the third clinic series study of 22 renal carcinoma patients, 3 patients
responded with disappearance and greater than 50% shrinkage of lung
lesions. None of these 3 responders had received previous treatment8.

Because the fourth clinic series of 15 patients taking shark cartilage
conducted in Cuba was described on the TV program, "60 Minutes," but never
published, disease response and survival times cannot be reviewed9.

A phase I/II trial of safety and efficacy in 47 evaluable patients with a
variety of advanced cancers found 4 patients who had to stop because of
toxicity, 5 deaths, no significant improvement in quality of life, and no
partial or complete responses at 12 weeks10.

Shark cartilage for oral use was evaluated in two separate phase II studies
for patients with metastatic prostate (n=12) or breast cancer (n=20) that
was refractory to standard treatments. Patients had to remain on study for
at least two months to be evaluable. Of the 10 evaluable patients with
prostate cancer, there were 3 with stable and 7 with progressive disease.
Of the 10 patients with breast cancer, there were 2 with stable and 8 with
progressive disease. There were no significant changes in performance
status, quality of life, or pain scores for patients in either the prostate
or breast groups11.

A phase II study of 14 stage 4 breast cancer patients reported that of the
4 who have completed 20 weeks of treatment with shark cartilage, 2 show no
response, 1 is stable, and 1 has reduced neck metastasis and eliminated
lung metastasis5. 

The final clinic series was a phase I trial of 77 lung and prostate
non-responsive cancer patients treated with varying doses of Neovastat.
Results suggest a positive trend in favor of a dose/response effect of
patients’ clinical benefits and tumor mass stabilization at doses of 30-50
mg/kg6.

The best case series included late stage cancer patients using shark
cartilage. Of the 21 patients, 61% reported reduced tumor size and 87%
reported improved quality of life. All 7 prostate patients reported a
reduced PSA level. It should be noted that these patients may have taken
cartilage in conjunction with other natural therapies12.

*See legend for design, result, and outcome coding.



 
Bib#



 
Design



 
Sites



Number Patients



 
Stage

Patient
Characteristics 
TreatmentOutcome
Assessed 
Results

1



CS
vs
BC



Numerous



31



Local ± ext Regional or distant

Large tumors +/- mets. Had failed conventional therapy. Complied with
cartilage treatment.Catrix p.o. (8g/d) and Catrix-S s.q. injection (100
ml/day)

DR

CR-19; PR-10; None-2

7



CS



Colon, renal & other



9



Distant non-brain mets

Previous conventional therapyCatrix-S injection 100ml/wk
3 wks 150 ml/wk>=4wks.

DR

8 progressive disease

8



CS



Renal



22



Distant

Catrix p.o. (3g/d 30 days). Catrix 5Q s.g. injections:

DR

3/22 with disappearance and >50% shrinkage of lung lesions.

9



CS



Unknown



15

Catrix p.o. and rectal

DR

½ are still alive at time of report

12



BC



Various



21



Late stage

Shark cartilage users

Survival & DR

61% reduced tumor size. 87% improved quality of life

10



CS



Various



58 (47 evaluable)



Advanced

Life expectancy of 12 wks, ECOG performance 0-2, no other anticancer
therapy, no prior cartilage.1g/kg of oral shark cartilage per day

DR

no partial or complete responses

11



CS



Breast



20 (10 evaluable)



Metastatic

Measurable disease that had progressed after at least 2 chemo regimens1g/kg
of oral shark cartilage in 4 divided doses per day

DR

2 stable disease at 8 and 20 weeks; 8 progressive disease.

11



CS



Prostate



12 (10 evaluable)



Metastatic

Measurable disease or bone only mets or rising PSA that progressed after at
least 2 hormone trmts.1g/kg of oral shark cartilage in 4 divided doses per
day

DR

3 stable disease at 20 and 24 & 28 weeks; 7 progressive disease.

5



CS



Breast



14 (4 evaluable)



Stage 4

Non-responsive, terminal patients off all therapies for at least 3
weeks1g/kg or oral shark cartilage taken 3-4 times per day

DR

2 no response; 1 stable;

1 reduced neck mets and eliminated lung mets



6



CS



Lung & prostate



77

Refractory and no longer responding to conventional treatmentProgressively
higher doses of Neovastat

DR

Positive trend in favor of highest dose.

*Legend

CODESTUDY DESIGNCODERESPONSE OR OUTCOMERCTRandomized Clinical TrialCR
Complete ResponsePCo/IntProspective Cohort with Internal Controls PRPartial
ResponseRRRetrospective ReviewSDStable DiseasePCo/HistProspective Cohort
with Historical ControlsDPDisease ProgressionPCo/NoProspective Cohort with
No ControlsOSObjective StabilizationCCCase ControlORObjective
ResponseCSClinical SeriesMRMixed ResponseBCBest CasesPOS RPositive
ResponseCRCase ReportDTDiscontinued TreatmentRCo/HistRetrospective Cohort
with Historical ControlsUUnknownPco/ExtProspective Cohort with External
ControlsEXPExpired  DRDisease Response  SSurvival

Proposed Mechanism of Action (Pharmacology)

Theories concerning the mechanism of action for shark and bovine cartilage
differ. For bovine cartilage, Prudden states that the action is due to the
active muco polysaccharide (large sugar molecules) that acts on tumor cell
membranes to block mitosis (cell division). Unpublished observations by
A.G. Johnson cited by Prudden1 report general activation of and increase of
macrophages and activation of cytotoxic T and B cells. The increase in B
cells increases immunoglobulins A, G, and M, resulting in an overall
increase in anti-mitotic activity; and increase may also be found in NK
cells. Further, the immuno-stimulatory activity reduces the size of
aberrant cells. 

In contrast, the proposed mechanism of action for shark cartilage is
anti-angiogenesis. Langer identified the antiangiogenesis factor as a
peptide that is destroyed by digestion, and thus, unlikely to be effective
if taken orally which is the usual route for shark cartilage. As per Boik
(page 164)4, Gardner "…found that large polypeptides do pass through the
stomach and intestines undigested and that the terminal stages of protein
digestion occur intracellularly in the mucosal absorptive cells of the
intestinal lining; small amounts of intact proteins and peptides do enter
the circulation under normal conditions. Peptide transport systems,
distinct from free amino acid transport, have been identified in intestinal
brush-border membranes, but the degree that peptides are able to enter the
circulation is considered limited."

Lane cites the study by Lee and Langer13 which reports that shark cartilage
is 1000 times more potent as an angiogenic inhibitor than bovine; since it
takes 500 grams of calf cartilage to produce 1 milligram of
‘cancer-inhibiting extract’ versus 0.5 grams of shark cartilage to produce
the same amount of active extract - a ratio of 1 to 100014. Folkman,
however, used over one ton of shark cartilage to extract a few micrograms
(millionths of a gram) for experiments with mice15. Langer showed that
bovine cartilage does have less of an anti-angiogenic effect than shark
cartilage on tumors transplanted into the eye16. 

In August, l998, a large manufacturer of shark cartilage (Aeterna
Laboratories) announced the isolation of an compound from shark cartilage
with anti-matrix metalloprotease (MMP) inhibition properties. The MMP
enzyme assists cancer cells to metastases by degrading the inter-cellular
structure 17.

In contrast, Prudden states that the most important active principle is the
immunostimulating effect on macrophages. Following this theory, it takes 9
grams of bovine to achieve therapeutic levels versus 70 grams (1/2 gram per
pound of body weight) for shark; therefore, the ratio of 8 to 1 in favor of
bovine cartilage for immunostimulation. 

Holistic Approach? 

No

Possible Toxicity

Catrix has been given in very high doses with minimal or no side effects.
It is apparently less toxic than many chemotherapies. However, since
Catrix-S is formulated for injection, issues of sterility and contamination
are critical. In addition, occasional serious reactions to the injectable
form of Catrix-S such as allergic reactions to traces of bovine protein may
be expected to occur. The possibility of contamination of individual
batches exists and should be carefully monitored at the existing
manufacturing sites. 

A possible complication of shark cartilage could be the excessive amount of
calcium at 22% which with a daily dose of 70 grams results in 14 grams of
calcium, or 14 times that recommended by the USRDA. 

No serious side effects were reported in the Phase I trial of 77 patients
by Aeterna Laboratories, Inc6.


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