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This cancer information summary provides an overview of the use of cartilage as a treatment for people with cancer. The summary includes a brief history of cartilage research, the results of clinical studies, and possible side effects of cartilage use.
This summary contains the following key information:
Many of the medical and scientific terms used in this summary are hypertext linked (at first use in each section) to the NCI Dictionary of Cancer Terms, which is oriented toward nonexperts. When a linked term is clicked, a definition will appear in a separate window.
Reference citations in some PDQ cancer information summaries may include links to external websites that are operated by individuals or organizations for the purpose of marketing or advocating the use of specific treatments or products. These reference citations are included for informational purposes only. Their inclusion should not be viewed as an endorsement of the content of the websites, or of any treatment or product, by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board or the National Cancer Institute.
Bovine (cow) cartilage and shark cartilage have been investigated as treatments for people with cancer, psoriasis, arthritis, and a number of other medical conditions for more than 30 years.[
The absence of blood vessels in cartilage led to the hypothesis that cartilage cells (also known as chondrocytes) produce one or more substances that inhibit blood vessel formation.[
The major structural components of cartilage include several types of the protein collagen and several types of glycosaminoglycans, which are polysaccharides.[
Some glycosaminoglycans in cartilage reportedly have anti-inflammatory and immune-system -stimulating properties,[
Cartilage products are sold commercially in the United States as dietary supplements. More than 40 different brand names of shark cartilage alone are available to consumers.[
To conduct clinical drug research in the United States, researchers must file an Investigational New Drug (IND) application with the FDA. IND status has been granted to at least four groups of investigators to study cartilage as a treatment for people with cancer; one of these trials, MDA-ID-99303, is now completed.[
In animal studies, cartilage products have been administered in a variety of ways. In some studies, oral administration of either liquid or powdered forms has been used.[
In human studies (MDA-ID-99303, AETERNA-AE-MM-00-02, and NCCTG-971151), cartilage products have been administered topically or orally, or they have been given by enema or subcutaneous injection.[
In this summary, the brand name (i.e., registered or trademarked name) of the cartilage product(s) used in individual studies will be identified wherever possible.
The therapeutic potential of cartilage has been investigated for more than 30 years. As noted previously (refer to the General Information section of this summary for more information), cartilage products have been tested as treatments for people with cancer, psoriasis, and arthritis. Cartilage products have also been studied as enhancers of wound repair and as treatments for people with osteoporosis, ulcerative colitis, regional enteritis, acne, scleroderma, hemorrhoids, severe anal itching, and the dermatitis caused by poison oak and poison ivy.[
Early studies of cartilage's therapeutic potential utilized extracts of bovine (cow) cartilage. The ability of these extracts to suppress inflammation was first described in the early 1960s.[
The first report that shark cartilage contains at least one angiogenesis inhibitor was published in the early 1980s,[
As indicated previously (refer to the Overview and General Information sections of this summary for more information), at least three different mechanisms of action have been proposed to explain the anticancer potential of cartilage: 1) it is toxic to cancer cells; 2) it stimulates the immune system; and 3) it inhibits angiogenesis. Only limited evidence is available to support the first two mechanisms of action; however, the evidence in favor of the third mechanism is more substantial (refer to the Laboratory/Animal/Preclinical Studies section of this summary for more information).
The process of angiogenesis requires at least four coordinated steps, each of which may be a target for inhibition. First, tumors must communicate with the endothelial cells that line the inside of nearby blood vessels. This communication takes place, in part, through the secretion of angiogenesis factors such as vascular endothelial growth factor.[
Cartilage is relatively resistant to invasion by tumor cells,[
The antitumor potential of cartilage has been investigated extensively in laboratory and animal studies. Some of these studies have assessed the toxicity of cartilage products toward cancer cells in vitro.[
Powdered Cartilage Products
In one study, cells from 22 freshly isolated human tumors (nine ovary, three lung, two brain, two breast, and one each of sarcoma, melanoma, colon, pancreas, cervix, and testis) and three human cultured cell lines (breast cancer, colon cancer, and myeloma) were treated with Catrix, which is a commercially available powdered preparation of bovine (cow) cartilage.[
A commercially available preparation of powdered shark cartilage (no brand name given) was reported to have no effect on the growth of human astrocytoma cells in vitro.[
The immune system –stimulating potential of cartilage has also been investigated in laboratory and animal studies.[
The effects of shark cartilage on the immune system were also reported in two studies that used the same purified protein fraction that had exhibited the most immunostimulatory effects when tested.[
Additional in vivo studies of the antitumor potential of shark cartilage have been published in the peer-reviewed scientific literature.[
A large number of laboratory and animal studies concerning the antiangiogenic potential of cartilage have been published.[
Aqueous Extracts of Cartilage
A liquid (i.e., aqueous) extract of shark cartilage called AE-941/Neovastat has also been reported to inhibit the growth of a variety of cancer cell types in vitro.[
Three angiogenesis inhibitors in bovine cartilage have been very well characterized.[
A possible fourth angiogenesis inhibitor in bovine cartilage has been purified not from cartilage but from the culture fluid of bovine chondrocytes grown in the laboratory.[
As indicated previously, shark cartilage, like bovine cartilage, contains more than one type of angiogenesis inhibitor. One shark cartilage inhibitor, named U-995, reportedly contains two small proteins, one with a molecular mass of approximately 14,000 and the other with a molecular mass of approximately 10,000.[
The second angiogenesis inhibitor identified in shark cartilage appears to have been studied independently by three groups of investigators.[
Other studies have demonstrated that AE-941/Neovastat, the previously mentioned aqueous extract of shark cartilage, has antiangiogenic activity,[
The cartilage-derived antiangiogenic substance troponin I (TnI) has been isolated from human cartilage and has been produced by the cloning and expression of cDNA of human cartilage. It has been shown to specifically inhibit angiogenesis in vivo and in vitro and tumor metastasis in vivo.[
Since the early 1970s, at least a dozen clinical trials (MDA-ID-99303, NCCTG-971151, and AETERNA-AE-MM-00-02) of cartilage as a treatment for people with cancer have been (or are being) conducted;[
In the first 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.[
Powdered Cartilage Products
Two of the three published clinical studies evaluated the use of Catrix, the previously mentioned (refer to the Laboratory/Animal/Preclinical Studies section of this summary for more information) powdered preparation of bovine (cow) cartilage, as a treatment for various solid tumors.[
In the case series,[
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,[
The third published study of cartilage as a treatment for people with 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.[
Partial results of three other clinical studies of powdered shark cartilage are described in two abstracts submitted for presentation at scientific conferences,[
Aqueous Extracts of Cartilage
In the phase II trial,[
The safety and the efficacy of AE-941/Neovastat, the previously mentioned aqueous extract of shark cartilage, has also been examined in clinical studies.[
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.[
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.[
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.[
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.[
In 2010, the results of a randomized, double-blind, placebo-controlled phase III trial aimed at assessing the effect of adding AE-941 to chemotherapy and radiation therapy on the overall survival of patients with nonresectable stage III NSCLC were reported. A total of 379 eligible patients received induction chemotherapy followed by concurrent chemotherapy with chest radiation therapy; participating centers used one of two chemotherapy regimens, either carboplatin and paclitaxel, or cisplatin and vinorelbine. No statistically significant difference in overall survival was observed between the group (n = 188) receiving chemotherapy and radiation therapy plus AE-941 (120 mL administered orally twice daily) and the group receiving chemotherapy and radiation therapy plus placebo (n = 191). Both AE-941 and placebo were well tolerated.[
|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|
|No. = number; NSCLC = non-small cell lung cancer; wk = week.|
|a See text and theNCI Dictionary of Cancer Termsfor additional information and definition of terms.|
|b Other clinical studies have been conducted, but no results have been reported.|
|c Strongest evidence reported that the treatment under study has anticancer activity or otherwise improves the well-being of cancer patients.|
|d Chemotherapy, radiation therapy, hormonal therapy, or cytokine therapy given/allowed at the same time as cartilage therapy.|
|e For information about Levels of Evidence analysis and an explanation of the level of evidence scores, see Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.|
|f Study results reported in review article or abstract form only; insufficient information presented for Level of Evidence analysis.|
|g Insufficient information available to describe these studies separately.|
||Phase III randomized, placebo-controlled, double-blind trial (2 arms)||Breast and colorectal||BeneFin (shark)||42; 41||No statistically significant difference||No||1i|
||Randomized controlled phase III trial||NSCLC||AE-941 (shark)||188; 191||None||Cisplatin and vinorelbine; carboplatin and paclitaxel||1iA|
||Nonconsecutive case series||Various advanced or recurrent||Catrix (bovine)||31; None||Complete response, 19 patients||Yes||3iiiDiii|
||Phase II trial||Various metastatic||Catrix (bovine)||9; None||Complete response, 1 patient, metastatic renal cell carcinoma||No||3iiiDiii|
||Phase II trial||Metastatic renal cell||Catrix (bovine)||35; None||Partial response, 3 of 22 evaluable patients||Unknown||Nonef|
||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|
||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|
||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|
||Phase II trial||Metastatic, refractory breast||Unknown (shark)||20; None||Stable disease for 8 wk or more, 2 of 10 evaluable patients||No||Nonef|
||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|
||Phase II trial||Various advanced brain||BeneFin (shark)||12; None||Stable disease for 20 wk or more, 2 of 10 evaluable patients||No||Nonef|
The side effects associated with cartilage therapy are generally described as mild to moderate in severity. Inflammation at injection sites, dysgeusia, fatigue, nausea, dyspepsia, fever, dizziness, and edema of the scrotum have been reported after treatment with the bovine (cow) cartilage product Catrix.[
Although at least a dozen clinical studies of cartilage as a treatment for people with cancer have been conducted since the early 1970s, relatively few results have been reported in the peer-reviewed scientific literature. There are small amounts of reported data from phase III clinical trials. Additional clinical studies are now under way. At present, the use of cartilage (bovine [cow] or shark) as a treatment for people with cancer cannot be recommended outside the context of well-designed clinical trials.
Separate levels of evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and scientific strength of the treatment outcomes (i.e., endpoints) measured. The resulting two scores are then combined to produce an overall score. For additional information about levels of evidence analysis, refer to Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
This summary is written and maintained by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the use of cartilage (bovine and shark) in the treatment of people with cancer. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
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Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Integrative, Alternative, and Complementary Therapies Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
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The preferred citation for this PDQ summary is:
PDQ® Integrative, Alternative, and Complementary Therapies Editorial Board. PDQ Cartilage (Bovine and Shark). Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/treatment/cam/hp/cartilage-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389205]
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Last Revised: 2018-08-23
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