Simone Shark Cartilage Protocol

Art Flatau, a patient, was kind enough to send me a copy of Charles B. Simone, M.D.’s protocol for the treatment of advanced cancer with shark cartilage. Because of the intense interest in Shark Cartilage, I have typed up most of it and am posting it here. The protocol also contains some information on Bovine Cartilage. I believe that Bovine Cartilage is far more promising and far better documented than Shark Cartilage. If you are considering cartilage therapy, I recommend that you take a look at my detailed write up of Bovine Cartilage.

A protocol is the documented design for a clinical trial. As such it contains details on administration of therapy among other things, as well as valuable information on the history of shark cartilage as a theraputic agent. This protocol is apparently approved by the NIH’s alternative medicine office. I have summarized the protocol here by deleting sections which are not essential to understanding the background or Simone’s treatment regimen. If anyone with advanced cancer is interested in using Shark Cartilage, I would strongly suggest that they get in touch with Dr. Simone at:

Simone Protective Cancer Center
123 Franklin Corner Road
Lawrenceville, NJ 08648

I.W. Lane in his book “Sharks Don’t Get Cancer” makes the point that one could use Shark Cartilage with any other therapy without conflict, so people considering trying this not-well-proven remedy need not abandon other therapy they may be taking, and indeed they ought not abandon any therapy of proven value in favor of Shark Cartilage.

In the below protocol dated May 1993, items in [], are my comments. Numbers in () refer to references cited at the end.

1. Introduction
[Deleted - a summary of our lack of progress in fighting cancer over the
last few decades].
2. Background
Cartilage has been used since the 1950s for the promotion of wound
healing (9-10). Bovine cartilage has been administered both orally and
parenterally (11) for the treatment of osteoarthritis, acute and chronic
skin allergies, psoriasis, rheumatoid arthritis, ulcerative colitis,
regional enteritis, and progressive systemic sclerosis. It has been shown
in these studies to have potent anti-inflamatory and antiallergic properties.
In 1963, it was postulated that tumors were dependent upon angiogenesis
(12). As the tumor grows, there is an increase in new capillaries that
converge upon the tumor every time there is an increase in tumor cell
population (13). Both bovine and shark cartilage were found to contain
inhibitors of tumor angiogenesis. Shark cartilage contains many of the
same biochemical activities as bovine cartilage including, lysozyme
activity, cell growth promoting activity [This sounds BAD!], inhibitory
activity against type I collagenase [I believe collagenases are involved
the mechanisms of metastasis and invasion], inhibitory activity against
proteases such as trypsin, chymotrypsin, plasmin (14,15).
The angiogenic factors of various species were identified, purified,
amino acid sequence determined, and their genes coded. The polypeptides
identified included acidic and basic fibroblast growth factor,
angiogenin, and transforming growth factors alpha and beta (16).
Shark cartilage has been used to treat osteoarthritis and solid tumors in
animal and human studies (17-19). Other investigators continued
experiments on angiogenisis, its inhibitors and cartilage activity
against cancer in vitro, animals, and in humans (20-25). In addition,
some non-neoplastic diseases have persistent angiogenesis as their
dominant pathology. These diseases include diabetic retinopathy,
retrolental fibroplasia, and neovascular glaucoma, rheumatoid arthritis,
hemangiomas, psoriasis, angiofibromas. (26-31).
In 1985, an investigator reported on the use of bovine cartilage in the
treatment of 31 patients most of whom had advanced cancers. (32) The
following responses were reported: a complete response for 35 percent,
complete response with relapse in 26 percent, partial response in 19
percent, partial response with relapse in 10 percent, and no change or
progression in 9 percent. The patients studied had cancers of the breast,
ovary, cervix, prostate, leiomyosarcoma of the left broad ligament,
colorectal, gastric, pancreas, lung, Hodgkins, renal, glioblastoma, basal
and squamous cell of the skin.
The size of the inhibitory angiogenesis factors from shark cartilage has
ranged from molecular weights of 1000 to 20,000 daltons or more. Both the
shark cartilage and bovine cartilage has been administered enterally in
human and animals. It has been shown that the intestinal membrane is
permeable to macromolecules of up to about 50,000 daltons (33-35) and
hence the antiangiogenesis factors should readily pass as indicated by
the positive responses seen, but there have been no pharmacological
studies or kinetic studies of the cartilages in humans. [This point is
contraversial - I belive most people don't think proteins pass the
intestine in significant amounts]
The following animal and human studies using shark cartilage preceded the
Cuban trial [That was reported on in 60 minutes]. Tumor regression was
shown by Atassi of human xenografts in nude mice at an oral dose of
1200mg per kilogram. Giving 150mg per kilogram of shark cartilage to 16
dogs resulted in improvement of their osteoarthritis. And administering
an oral dose of 12 capsules containing 740mg produced symptomatic relief
in 5 of 6 patients with osteoarthritis as reported by Ng at the
University of Miami, School of Medicine. Six of eight patients with
advanced cancer treated at a Mexican clinic showed tumor regression when
given 30gm per day of shark cartilage intrarectally or intravaginally.
Nineteen evaluable patients with advanced cancers were treated in Cuba
using 70-100gm of rectally administered shark cartilage per day. I
[Simone] personally was present to examine the patients and the data at
week 6, week 16 and week 20. I did not see the patients at day 1 of week
1. But at week 6, twelve patients had regression, one continued to have
tumor growthm and six patients were unevaluable, (too near deathm no
followable diseasem or no evidence of disease at that time). At week 16,
however, four patients continued to have regression of disease, seven
started to regrow, two patients were unevaluable, and five were dead, one
was stable. At week 20 these numbers remained the same. The patients had
the following cancers: prostate cancer metastatic to bone, esophageal
cancer, ovarian cancers metastatic to liver or lung, colon cancer
metastatic to liver, primary hepatoma, and two astocytomas, one grade 2
and one grade 4. Those patients who had a response at week 20 included: 2
patients with ovarian cancer metastatic to liver and pleura; one patient
with astrocytoma grade 2 status post 80% resection but who has cranial
nerve VII palsy post-op which resolved completely as well as complete
resolution of equilibrium with no other treatment; and one patient with
prostate cancer metastatic to bone.
Unlike fumagillin and its analogs, petosan, heparin-cortisone
combinations, and other angiogenesis inhibitors, (38) there has been no
reported toxicities of shark cartilage or bovine cartilage. Both are
obtained in powder form or in capsule form.
3. Objectives
To further evaluate the potential efficacy of shark cartilage and bovine
cartilage in the treatment of advanced human cancers.
4. Study Design
Patients with any advanced cancers will be studied. They will be
clinically evaluated weekly and objectively at week 6 and 12 with
laboratory or imaging work-up. The use of cartilage will be discontinued
of tumor progression is demonstrated between weels 8 and 12; or it
clinical events dictate.
Each patient will also be instructed on the Simone Ten Point Plan [See
his book Nutrition and Cancer] which will ideally be implemented in every
patient. The patients are to follow the pertinent applicable points of
the Ten Point Plan. The Ten Point Plan is as follows:
4.1 Nutrition
Ensure proper caloric intake to maintain or increase the patient's ideal
weight. The diet is to be supplemented with certain vitamins and minerals
especially the antioxidants. Beta Carotene 30mg; Vitamin A 5,000IU;
Vitamin D 400IU; Vitamin E 400IU; Vitamin C 350mg; Folic Acid 400mcg;
Vitamin B1 10mg; Vitamin B2 10mg; Niacinamide 40mg;  Vitamin B6 10mg;
Vitamin B12 18mcg; Biotin 150mcg; Pantothenic Acid 20mg, Iodine 150mcg,
Copper 3mg; Zinc 15mg; Potassium 30mg; Selenium 200mcgl Chromium 125mcg;
Maganese 2.5mg; Molybendum 50mcg; Inositol 10mg;  ParaAminoBenzoic Acid
1mg; Arginine 5mg.
4.2 Tobacco - Do Not Smoke, Chew, Snuff, or inhale other people's smoke.
4.3 Alcohol - Avoid all alcohol
4.4 Radiation - X-Rays only when needed. Use sunscreens.
4.5 Environment - Avoid unhealthy air, water, and electromagnetic fields.
4.6 Hormones, Drugs - Avoid unnecessary hormones and drugs
4.7 Seven Warning Signs of Cancer - Learn them
4.8 Review symprtoms of organ involvement.
4.9 Exercise as tolerated and Relax regularly
4.10 Physical Exam routinely
[I think much of this is vague, irrelevant, and complicates the study
design, although much is also sensible advice.]
5. Chemical Composition of Shark Cartilage To Be Used
["Selachii 490" Selachii Distributors, Mission Kansas, 66201 800-334-7777]
Component                    Approximate Percentage
Protein                      38%
Carbohydrates                6%
Ash                          52%
Calcium                      18%
Phosphorus                   9%
Moisture                     6%
[Has a biological assay (CAM assay) of antiangiogenic activity been conducted
on this brand of shark cartilage?]
6. Patient Selection Criteria
Patients must have:
*at least a 12? week life expectancy
*histological diagnosis of cancer and prior treatment (except for
renal cancer and melanoma) using surgery, chemotherapy, or radiation
therapy; and despite this tumor continues to grow.
*objective measurable disease
*baseline evaluation of CBC with differential, chemistry screening,
and any pertinent screen markers or imaging studies prior to
the initiation of cartilage.
*signed informed consent which they understand
6.1 Exclusion Critera
*Radiation therapy to brain for primary brain tumor within 45
days prior to enrollment.
*Use of cartilage concomitant with any other therapy
6.2 Patient Discontinuation
The investigator may discontinue a patient from the study at any
time when the physician believes this is in the best interest of the
patient; Several examples include: progressive disease, patient's
desire to withdraw from the study, or patient's noncompliance, etc.
6.3. Definitions
[Deleted - standard oncology definitions of complete and partial
response, stable disease, and progressive disease]
[Deleted - Plan to measure subjective response/Quality of life with
a questionnaire]
7. Treatment Plan
All eligible patients will use shark cartilage with the chemical
composition described previously. Starting dose is 70gm based on the Cuban
trial. It can be self administered either orally or rectally. [??? is this
the patient's choice - this variable should be controlled!]
Oral administration: 3 divided doses, 4 level teaspoons in the morning, 5
level teaspoons in the afternoon, and 5 level teaspoons at night. Each
dose should be given just prior to ingestion of food in juice. The
cartilage will not dissolve, so it must be stirred until all is ingested,
juice ad libitum.
Rectal Administration: Two doses each approximately containing 35gm to be
put in one-third to one-half water and administered rectally. The patient
is then to lay on his/her left side for approximate[ly] 30 minutes to
allow for absorbtion.
If there is no apparent response at week 6, the dose will be escalated to
90 gm per day of shark cartilage.
Bovine cartilage will be used in patients who have the following cancers:
lung, breast, brain, colon, and prostate. Every third protocol patient
with one of these cancers will recieve bovine cartilage. The dose will be
9 gm administered orally every day in three divided doses. (39) [This is
in addition to the shark cartilage].
8. Study Schedule
[Deleted - schedule for studies/interviews etc. One notable thing is that
apparently, patients who are already taking cartilage will be allowed on
study - this is bizzare!]
9. Withdrawal from Study
[Deleted - standard verbage about patient right to withdraw,
confidentiality etc].
10. International Physician Network
We will be recruiting physicians from America and around the world to
administer this protocol and others in the future. Through the
International Physician Network, we will quickly be able to recruit
hundreds of patients to scientifically determine if cartilage or any
other treatment is efficacious. [Interested Physicians take note!]
[IMHO, as a layman, this protocol is not nearly as well specified or
designed as protocols I have seen for conventional clinical trials. The
end points are not well defined, the number of patients to be accrued is
not defined, along with other problems I noted in the text. Still, if
they are careful in documenting responses, it seems to me that they
should be able to tell whether shark cartilage works some of the time]
[1-8 Deleted - general refs on cancer stats]
9. Prudden, John et al. 1957. The acceleration of wound healing with
cartilage. Surg. Gynecol Obstet. 105:283.
10. Prudden, John. 1965. The clinical acceleration of healing with a
cartilage preparation: A controlled study. JAMA. 192:252.
11. Prudden, John and Balessa. 1974. The biological activity of bovine
cartilage perparations. Seminars in Arthritis and Rheumatism. Vol 3
12. Folkman, J. et al. 1963. Cancer 16:453.
13. Folkman, J 1971. NEJM 285:1182.
14. Folkman, J. 1976. Isolation of a cartilage factor that inhibits tumor
neovascularization. Science. 193:70-71.
15. Lee, A. and Robert Langer. 1983 Shark cartilage contains inhibitors
of tumor angiogenesis. Science. 221:1185-1187
16. Folkman, J. abd Klagsburn, M. 1987. Angiogenic factors. Science.
17. Atassi, G. 1989. Sept 1. Investigation of the antitumor effect of
shark cartilage on human xenografts in nude mice. Institute Jules Bordet.
Brussels. (Unpublished). [Grrrrr...]
18. Lane, I.W., E. Contreras [Famed latrile... dare I say quack]. 1992
High rate of bioactivity observed in cancer patients treated with shark
cartilage material. J. Naturopathic Medicine. 3(1):86-88.
19. Rauis, J. 1991. Use of shark cartilage in the treatment of secondary
osteoarthritis in the dog. British Small Animal Association Congress,
United Kingdom.
20. Stetler-Stevenson, Wm. Biological basis for neoadjuvant and adjuvant
therapy: tumor invasion and metastasis (TIMP's). Neoadjuvant and Adjuvant
Therapy for Selected Malignancies. Mar 5, 1993. UMDNJ.
21. D'Amore, P. 1988. Angiogenesis as a strategy for antimetastasis.
Seminars in Thrombosis and Hemostasis. 14(1):73-78
22. D'Amore and Klagsbrun. 1989. Angiogenesis factors and mechanisms from
the pathobiology of neoplasia. Edited Alphonse E. Sirica. Plenum Pub Corp
23. Moses, M., Sudhalter, Langer 1990. Identification of an inhibitor of
neovascularization from cartilage. Science 248:1408-1410.
24. Pauli, et al. 1981. Regulation of tumor invasion with cartilage derived
inhibitor in vitro. JNCI 67:65-63[???]
25. Sadova, et al. 1977. Inhibition of mammary carcinoma invasiveness
with cartilage derived inhibitor. Surgical Forum. 28499-501.
26. Brim, H.J. Folkman. 1975. An inhibition of tumor angiogenesis
mediated by cartilage. J Ex Med 141:427-39.
27. Moses et al. 1990. Identification of an inhibitor of
neovascularization from cartilage. Science. 248:4961 p. 1408-1410.
28. Pepper et al. 1991. Chondrocytes inhibit endothelelial sprout
formation in vitro: evidence for involvement of transforming factor beta.
J. Cell. Physiol. 146(1):170-9.
29. Takigawa et all. 1990. A clonal human chondrosarcoma cell line
produces an anti-angiogeneic antitumor factor. Antocancer Research.
30. Takigawa. et al. 1987. A factor and condition medium of rabbit costal
chondrocytes inhibits the proliferation of cultured endothelial cells and
angiogenesis induuced by B16 melanoma: Its relation with
cartilage-derived antitumor factor. Biochem International. 14(2):357-63.
31. Oikawa, et al. 1990. A novel angiogeneic inhibitor derived from
Japanese shark cartilage. One extraction and estimation of inhibitory
activities towards tumor and embryonic angiogenesis. Cancer Letters.
32. Prudden, J. 1985. The treatment ofhuman cancer with agents derived
from bovine cartilage. J Biol Resp Modif. 4:551-84.
33. Warshaw, et al. 1971. Small intestinal permeability to
macromolecules: transmission of horseradish peroidase into mesenteric
lymph and portal blood. Lab Investigation. 25:675-84.
34. Warshaw, et al. 1974. Protein uptake by the intestine: evidence of
intact maromolecules. Gastroenterology. 66:987-92.
35. Williams, EW, Hemmings. 1979 Intestinal uptake and transport of
proteins in the adult rat. Proceedings Royal Society London. Br. 203:177-89.
36. Lane. Ibid
37. Contreras. Ibid.
38. Folkman and Ingber. 1992. Inhibition of angiogenesis. Seminars Cancer
39. Prudden, John. 1993. Personal Communication

This CancerGuide Page By Steve Dunn. © Steve Dunn
Last Updated: Mar 30, 1995