Powdered Cartilage Products
Aqueous Extracts of Cartilage

Since the early 1970s, at least a dozen clinical studies (MDA-ID-99303 ¹, NCCTG-971151 ², and AETERNA-AE-MM-00-02 ³) of cartilage as a treatment for cancer have been (or are being) conducted;[1-9] Reviewed in [10-16] (refer to the table ⁴ at the end of this section) however, results from only six studies have been published in peer-reviewed scientific journals.[1,2,4,8,9,17] It is not clear whether any of the patients in these studies were children.

In the only randomized trial published in a peer-reviewed scientific journal, 83 incurable breast cancer and colorectal cancer patients were randomly assigned to receive either shark cartilage or placebo, in addition to standard care. No difference was observed in survival or quality of life between those receiving shark cartilage and those receiving placebo.[8] Additional clinical studies are under way; however, the cumulative evidence to date is inconclusive regarding the effectiveness of cartilage as a cancer treatment.

Two of the three published clinical studies evaluated the use of Catrix, the previously mentioned (refer to the Laboratory/Animal/Preclinical Studies ⁵ section of this summary for more information) powdered preparation of bovine (cow) cartilage, as a treatment for various solid tumors.[1,2] One of these studies was a case series that included 31 patients;[1] the other was a phase II clinical trial that included 9 patients.[2]

In the case series,[1] all patients were treated with subcutaneously injected and/or oral Catrix; however, three patients (one with squamous cell carcinoma of the skin and two with basal cell carcinoma of the skin) were also treated with topical preparations. The individual dose, the total dose, and the duration of Catrix treatment in this series varied from patient to patient; however, the minimum treatment duration was 7 months, and the maximum duration was more than 10 years. Eighteen patients had been treated with conventional therapy (surgery, chemotherapy, radiation therapy, hormonal therapy) within 1 year of the start of Catrix treatment; nine patients received conventional therapy concurrently with Catrix treatment; and seven patients received conventional therapy both prior to and during Catrix treatment. It was reported that 19 patients had a complete response, 10 patients had a partial response, and 1 patient had stable disease following Catrix treatment. The remaining patient did not respond to cartilage therapy. Eight of the patients with a complete response received no prior or concurrent conventional therapy. Approximately half of the patients with a complete response eventually experienced recurrent cancer.

This clinical study had several weaknesses that could have affected its outcome, including the absence of a control group and the receipt of prior and/or concurrent conventional therapy by most patients.

Partial results of a third clinical study of Catrix are described in an abstract submitted for presentation at a scientific conference,[3] but complete results of this study have not been published in a peer-reviewed scientific journal. In the study, 35 patients with metastatic renal cell carcinoma were divided into four groups, and the individuals in each group were treated with identical doses of subcutaneously injected and/or oral Catrix. Three partial responses and no complete responses were observed among 22 evaluable patients who were treated with Catrix for more than 3 months. Following Catrix therapy, 2 of the 22 evaluable patients were reported to have stable disease, and 17 were reported to have progressive disease. No relationship between Catrix dose and tumor response could be established in this study.

The third published study of cartilage as a treatment for cancer was a phase I/II trial that tested the safety and the efficacy of orally administered Cartilade, a commercially available powdered preparation of shark cartilage, in 60 patients with various types of advanced solid tumors.[4] All but one patient in this trial had been treated previously with conventional therapy. According to the design of the study, no additional anticancer treatment could be given concurrently with Cartilade therapy. No complete responses or partial responses were observed among 50 evaluable patients who were treated with Cartilade for at least 6 weeks. However, stable disease that lasted 12 weeks or more was reported for 10 of the 50 patients. All ten of these patients eventually experienced progressive disease.

Partial results of three other clinical studies of powdered shark cartilage are described in two abstracts submitted for presentation at scientific conferences,[5,6] but complete results of these studies have not been published in peer-reviewed scientific journals. All three studies were phase II clinical trials that involved patients with advanced disease; two of the studies were conducted by the same group of investigators.[5] These three studies enrolled 20 patients with breast cancer,[5] 12 patients with prostate cancer,[5] and 12 patients with primary brain tumors.[6] All patients had been treated previously with conventional therapy. No other anticancer treatment was allowed concurrently with cartilage therapy. In two of the studies,[5] the name of the cartilage product was not identified; however, in the third study,[6] the commercially available product BeneFin was used. Ten patients in each study completed at least 8 weeks of treatment and therefore were considered evaluable for response. No complete responses or partial responses were observed in any of the studies. Two evaluable patients in the breast cancer study were reported to have stable disease that lasted 8 weeks or more; two evaluable patients in the brain tumor study had stable disease that lasted 20 weeks or more; and three evaluable patients in the prostate cancer study had stable disease that also lasted 20 weeks or more.

In the phase II trial,[2] Catrix was administered by subcutaneous injection only. All patients in this trial had progressive disease following radiation therapy and/or chemotherapy. Identical individual doses of Catrix were administered to each patient, but the duration of treatment and the total delivered dose varied because of disease progression or death. The minimum duration of Catrix treatment in this study was 4 weeks. One patient (with metastatic renal cell carcinoma) reportedly had a complete response that lasted more than 39 weeks. The remaining eight patients did not respond to Catrix treatment. The researchers in this trial also investigated whether Catrix had an effect on immune system function in these patients. No consistent trend or change in the numbers, percentages, or ratios of white blood cells (i.e., total lymphocyte counts, total T cell counts, total B cell counts, percentage of T cells, percentage of B cells, and ratio of helper T cells to cytotoxic T cells) was observed, though increased numbers of T cells were found in three patients.

The safety and the efficacy of AE-941/Neovastat, the previously mentioned aqueous extract of shark cartilage, has also been examined in clinical studies.[9,18] Reviewed in [11,10,16] It has been reported that AE-941/Neovastat has little toxicity. Reviewed in [10,11,16] In addition, there is evidence from a randomized clinical trial that examined the effect of AE-941/Neovastat on angiogenesis associated with surgical wound repair that this product contains at least one antiangiogenic component that is orally bioavailable.[18]

AE-941/Neovastat was administered to 331 patients with advanced solid tumors (including lung, prostate, breast, and kidney tumors) in two phase I/II trials. Reviewed in [10] The results of these trials, however, have not been fully reported. A retrospective analysis involving a subgroup of patients with advanced non-small cell lung cancer (NSCLC) suggests that AE-941/Neovastat is able to lengthen the survival of patients with this disease. Reviewed in [10] Furthermore, in a prospective analysis involving 22 patients with refractory renal cell carcinoma, survival was longer in patients treated with 240 mL /day AE-941/Neovastat than in patients treated with only 60 mL/day.[7,17] Reviewed in [10]

In 2003, the results of a phase I/II trial of AE-941/Neovastat in 80 patients with advanced NSCLC reported that there was a significant survival advantage for patients receiving the highest doses (2.6 mL/kg/day) of AE-941/Neovastat. A survival analysis of 48 patients with unresectable stage IIIA, IIIB, or IV NSCLC showed a median survival advantage of P = .0026 in patients receiving the highest doses. The trial was principally conducted to explore the safety and efficacy of orally administered AE-941/Neovastat when administered in escalating doses (30, 60, 120, and 240 mL/day). No dose-limiting toxicity was found, and no tumor response was observed.[9]

In 2001, a phase II trial (AETERNA-AE-MM-00-02) of AE-941/Neovastat was initiated in patients with relapsed or refractory multiple myeloma. This trial closed approximately 1 year later, and no results have been reported.[19]

Two randomized phase III trials of AE-941/Neovastat in patients with advanced cancer have been approved by the U.S. Food and Drug Administration (FDA). In one trial (MDA-ID-99303), which is completed, treatment with oral AE-941/Neovastat plus chemotherapy and radiation therapy was compared with treatment with placebo plus the same chemotherapy and radiation therapy in patients with stage III NSCLC. In the second trial, which closed to patient recruitment in 2002, treatment with oral AE-941/Neovastat was compared with treatment with placebo in patients with metastatic renal cell carcinoma. Results from this second phase III trial have not been reported in the peer-reviewed scientific literature.[20] Despite AE-941/Neovastat being granted orphan drug status by the FDA in 2002 for use in the treatment of renal cell carcinoma, the company that produces AE-941/Neovastat, Aeterna Laboratories, announced in early 2004 that this application would be discontinued in favor of a focus on the treatment of NSCLC.[20,21]

Cartilage Use in Cancer Treatment: Clinical Studies With Therapeutic Endpoints^a,b

Enlarge ⁶

Reference Citation(s)	Type of Study	Type(s) of Cancer	Cartilage Product (Source)	No. of Patients: Treated; Control	Strongest Benefit Reportedc	Concurrent Therapyd	Level of Evidence Scoree
[1]	Nonconsecutive case series	Various advanced or recurrent	Catrix (bovine)	31; None	Complete response, 19 patients	Yes	3iiiDiii
[2]	Phase II trial	Various metastatic	Catrix (bovine)	9; None	Complete response, 1 patient, metastatic renal cell carcinoma	No	3iiiDiii
[3]	Phase II trial	Metastatic renal cell	Catrix (bovine)	35; None	Partial response, 3 of 22 evaluable patients	Unknown	Nonef
[10,17]	Two phase I/II trialsg	Various advanced, refractory solid tumors	AE-941/ Neovastat (shark)	331; None	Improved survival, higher versus lower doses, patients with stage III/IV non-small cell lung cancer (unplanned retrospective analysis), and patients with refractory renal cell carcinoma (prospective analysis)	Unknown	Nonef
[9]	Phase I/II trial	Advanced non-small cell lung cancer	AT-941/Neovastat (shark)	80; None	No dose-limiting toxicity found. Improved survival time in patients receiving the highest doses when survival analysis was conducted, and stable disease for greater number of patients receiving higher doses. No tumor response observed.	Yes or refused standard therapy	None
[4]	Phase I/II trial	Various advanced solid tumors	Cartilade (shark)	60; None	Stable disease for 12 wk or more, 10 of 50 evaluable patients	No	3iiiDiii
[5]	Phase II trial	Metastatic, refractory breast	Unknown (shark)	20; None	Stable disease for 8 wk or more, 2 of 10 evaluable patients	No	Nonef
[5]	Phase II trial	Metastatic, hormone- refractory prostate	Unknown (shark)	12; None	Stable disease for 20 wk or more, 3 of 10 evaluable patients	No	Nonef
[6]	Phase II trial	Various advanced brain	BeneFin (shark)	12; None	Stable disease for 20 wk or more, 2 of 10 evaluable patients	No	Nonef
[8]	Phase III randomized, placebo-controlled, double-blind trial (2 arms)	Breast and colorectal	BeneFin (shark)	42; 41	No statistically significant difference	No	1i

No. = number; wk = week.

aSee text and glossary for additional information and definitions of most terms.

bOther clinical studies have been conducted, but no results have been reported.

cStrongest evidence reported that the treatment under study has anticancer activity or otherwise improves the well-being of cancer patients.

dChemotherapy, radiation therapy, hormonal therapy, or cytokine therapy given/allowed at the same time as cartilage therapy.

eFor information about Levels of Evidence analysis and an explanation of the level of evidence scores, see Levels of Evidence for Human Studies of Cancer Complementary and Alternative Medicine 7.

fStudy results reported in review article or abstract form only; insufficient information presented for Level of Evidence analysis.

gInsufficient information available to describe these studies separately.

References

1. Prudden JF: The treatment of human cancer with agents prepared from bovine cartilage. J Biol Response Mod 4 (6): 551-84, 1985.  [PUBMED Abstract]
   
   
2. Romano CF, Lipton A, Harvey HA, et al.: A phase II study of Catrix-S in solid tumors. J Biol Response Mod 4 (6): 585-9, 1985.  [PUBMED Abstract]
   
   
3. Puccio C, Mittelman A, Chun P, et al.: Treatment of metastatic renal cell carcinoma with Catrix. [Abstract] Proceedings of the American Society of Clinical Oncology 13: A-769, 246, 1994. 
   
   
4. Miller DR, Anderson GT, Stark JJ, et al.: Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer. J Clin Oncol 16 (11): 3649-55, 1998.  [PUBMED Abstract]
   
   
5. Leitner SP, Rothkopf MM, Haverstick L, et al.: Two phase II studies of oral dry shark cartilage powder (SCP) with either metastatic breast or prostate cancer refractory to standard treatment. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A-240, 1998. 
   
   
6. Rosenbluth RJ, Jennis AA, Cantwell S, et al.: Oral shark cartilage in the treatment of patients with advanced primary brain tumors. [Abstract] Proceedings of the American Society of Clinical Oncology 18: A-554, 1999. 
   
   
7. Batist G, Champagne P, Hariton C, et al.: Dose-survival relationship in a phase II study of Neovastat in refractory renal cell carcinoma patients. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1907, 2002. 
   
   
8. Loprinzi CL, Levitt R, Barton DL, et al.: Evaluation of shark cartilage in patients with advanced cancer: a North Central Cancer Treatment Group trial. Cancer 104 (1): 176-82, 2005.  [PUBMED Abstract]
   
   
9. Latreille J, Batist G, Laberge F, et al.: Phase I/II trial of the safety and efficacy of AE-941 (Neovastat) in the treatment of non-small-cell lung cancer. Clin Lung Cancer 4 (4): 231-6, 2003.  [PUBMED Abstract]
   
   
10. Falardeau P, Champagne P, Poyet P, et al.: Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials. Semin Oncol 28 (6): 620-5, 2001.  [PUBMED Abstract]
    
    
11. AE 941--Neovastat. Drugs R D 1 (2): 135-6, 1999.  [PUBMED Abstract]
    
    
12. Cassileth BR: Shark and bovine cartilage therapies. In: Cassileth BR, ed.: The Alternative Medicine Handbook: The Complete Reference Guide to Alternative and Complementary Therapies. New York, NY: WW Norton & Company, 1998, pp 197-200. 
    
    
13. Reviews of Therapies: Biologic/Organic/Pharmacologic Therapies: Cartilage. Houston, Tex: M.D. Anderson Cancer Center, 2003. Available online. ⁸ Last accessed September 16, 2009. 
    
    
14. Holt S: Shark cartilage and nutriceutical update. Altern Complement Ther 1: 414-16, 1995. 
    
    
15. Hunt TJ, Connelly JF: Shark cartilage for cancer treatment. Am J Health Syst Pharm 52 (16): 1756, 1760, 1995.  [PUBMED Abstract]
    
    
16. AE 941. Drugs R D 5 (2): 83-9, 2004.  [PUBMED Abstract]
    
    
17. Batist G, Patenaude F, Champagne P, et al.: Neovastat (AE-941) in refractory renal cell carcinoma patients: report of a phase II trial with two dose levels. Ann Oncol 13 (8): 1259-63, 2002.  [PUBMED Abstract]
    
    
18. Berbari P, Thibodeau A, Germain L, et al.: Antiangiogenic effects of the oral administration of liquid cartilage extract in humans. J Surg Res 87 (1): 108-13, 1999.  [PUBMED Abstract]
    
    
19. Ryoo JJ, Cole CE, Anderson KC: Novel therapies for multiple myeloma. Blood Rev 16 (3): 167-74, 2002.  [PUBMED Abstract]
    
    
20. Bukowski RM: AE-941, a multifunctional antiangiogenic compound: trials in renal cell carcinoma. Expert Opin Investig Drugs 12 (8): 1403-11, 2003.  [PUBMED Abstract]
    
    
21. New treatment option for postmenopausal women with early breast cancer. Expert Rev Anticancer Ther 2 (6): 617, 2002.  [PUBMED Abstract]
    
    

Glossary Terms

Blood vessel formation. Tumor angiogenesis is the growth of new blood vessels that tumors need to grow. This is caused by the release of chemicals by the tumor.

Having to do with reducing the growth of new blood vessels.

Having to do with water.

A type of immune cell that makes proteins called antibodies, which bind to microorganisms and other foreign substances, and help fight infections. A B cell is a type of white blood cell. Also called B lymphocyte.

A type of skin cancer that arises from the basal cells, small round cells found in the lower part (or base) of the epidermis, the outer layer of the skin.

The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body.

Cancer that forms in tissues of the breast, usually the ducts (tubes that carry milk to the nipple) and lobules (glands that make milk). It occurs in both men and women, although male breast cancer is rare.

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

A tough, flexible tissue that lines joints and gives structure to the nose, ears, larynx, and other parts of the body.

A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment.

Treatment with drugs that kill cancer cells.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical trial.

Cancer that develops in the colon (the longest part of the large intestine) and/or the rectum (the last several inches of the large intestine before the anus).

The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. Also called complete remission.

In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works.

A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment.

A type of immune cell that can kill certain cells, including foreign cells, cancer cells, and cells infected with a virus. Cytotoxic T cells can be separated from other blood cells, grown in the laboratory, and then given to a patient to kill cancer cells. A cytotoxic T cell is a type of white blood cell and a type of lymphocyte. Also called cytotoxic T lymphocyte and killer T cell.

The amount of medicine taken, or radiation given, at one time.

Effectiveness. In medicine, the ability of an intervention (for example, a drug or surgery) to produce the desired beneficial effect.

Patients whose response to a treatment can be measured because enough information has been collected.

A type of immune cell that stimulates killer T cells, macrophages, and B cells to make immune responses. A helper T cell is a type of white blood cell and a type of lymphocyte. Also called CD4-positive T lymphocyte.

Treatment that adds, blocks, or removes hormones. For certain conditions (such as diabetes or menopause), hormones are given to adjust low hormone levels. To slow or stop the growth of certain cancers (such as prostate and breast cancer), synthetic hormones or other drugs may be given to block the body’s natural hormones. Sometimes surgery is needed to remove the gland that makes a certain hormone. Also called endocrine therapy, hormone therapy, and hormone treatment.

The complex group of organs and cells that defends the body against infections and other diseases.

Use of a syringe and needle to push fluids or drugs into the body; often called a "shot."

A researcher in a clinical trial or clinical study.

A type of immune cell that is made in the bone marrow and is found in the blood and in lymph tissue. The two main types of lymphocytes are B lymphocytes and T lymphocytes. B lymphocytes make antibodies, and T lymphocytes help kill tumor cells and help control immune responses. A lymphocyte is a type of white blood cell.

Having to do with metastasis, which is the spread of cancer from the primary site (place where it started) to other places in the body.

A measure of volume in the metric system. One thousand milliliters equal one liter. Also called cc, cubic centimeter, and ml.

A type of cancer that begins in plasma cells (white blood cells that produce antibodies). Also called Kahler disease, myelomatosis, and plasma cell myeloma.

A group of lung cancers that are named for the kinds of cells found in the cancer and how the cells look under a microscope. The three main types of non-small cell lung cancer are squamous cell carcinoma, large cell carcinoma, and adenocarcinoma. Non-small cell lung cancer is the most common kind of lung cancer.

A clinical study that includes some, but not all, of the eligible patients identified by the researchers during the study registration period. This type of study does not usually have a control group.

By or having to do with the mouth.

A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. Also called partial remission.

A trial to study the safety, dosage levels, and response to a new treatment.

A study to test whether a new treatment has an anticancer effect (for example, whether it shrinks a tumor or improves blood test results) and whether it works against a certain type of cancer.

An inactive substance or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.

The original tumor.

Cancer that is growing, spreading, or getting worse.

In medicine, a study or clinical trial in which participants are identified and then followed forward in time.

Cancer that forms in tissues of the prostate (a gland in the male reproductive system found below the bladder and in front of the rectum). Prostate cancer usually occurs in older men.

The overall enjoyment of life. Many clinical trials assess the effects of cancer and its treatment on the quality of life. These studies measure aspects of an individual’s sense of well-being and ability to carry out various activities.

The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiotherapy.

Cancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body. Also called recurrence.

Cancer that does not respond to treatment. The cancer may be resistant at the beginning of treatment or it may become resistant during treatment. Also called resistant cancer.

The return of signs and symptoms of cancer after a period of improvement.

The most common type of kidney cancer. It begins in the lining of the renal tubules in the kidney. The renal tubules filter the blood and produce urine. Also called hypernephroma.

In medicine, an improvement related to treatment.

Looking back at events that have already taken place.

An abnormal mass of tissue that usually does not contain cysts or liquid areas. Solid tumors may be benign (not cancer), or malignant (cancer). Different types of solid tumors are named for the type of cells that form them. Examples of solid tumors are sarcomas, carcinomas, and lymphomas. Leukemias (cancers of the blood) generally do not form solid tumors.

Cancer that begins in squamous cells, which are thin, flat cells that look like fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma.

Cancer that is neither decreasing nor increasing in extent or severity.

Stage III is divided into stages IIIA and IIIB. In stage IIIA, cancer has spread to lymph nodes on the same side of the chest as the tumor; the tumor may be any size and cancer may have spread to the main bronchus, the chest wall, the diaphragm, the pleura around the lungs, or the membrane around the heart, but cancer has not spread to the trachea; and part or all of the lung may have collapsed or developed pneumonitis (inflammation of the lung). In stage IIIB, the tumor may be any size and has spread to lymph nodes above the collarbone or in the opposite side of the chest from the tumor; AND/OR to any of the following places: the heart, major blood vessels that lead to or from the heart, the chest wall, the diaphragm, the trachea, the esophagus, the sternum (chest bone) or backbone, to more than one place in the same lobe of the lung, and/or into the fluid of the pleural cavity surrounding the lung.

Beneath the skin.

A procedure to remove or repair a part of the body or to find out whether disease is present. An operation.

A type of immune cell that can attack foreign cells, cancer cells, and cells infected with a virus. T cells can also help control immune responses. A T cell is a type of white blood cell. Also called T lymphocyte and thymocyte.

On the surface of the body.

Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects.

A type of immune cell. Most white blood cells are made in the bone marrow and are found in the blood and lymph tissue. White blood cells help the body fight infections and other diseases. Granulocytes, monocytes, and lymphocytes are white blood cells. Also called leukocyte and WBC.