How well does shark cartilage work?
2.1 Pre-clinical studies
Some basic research studies have suggested direct toxicity against tumour cells. The inhibition of tumour angiogenesis has been relatively well documented in in-vitro studies One study, for instance, found that tamoxifen has significant anti-angiogenic activity that can be potentiated by shark cartilage. (ref 18)
A liquid shark cartilage extract, Neovastat, which is administered orally, was also found to have significant anti-tumour activity. Oral administration of Neovastat in mice with subcutaneous grafted breast cancer cells showed a significant reduction in tumour volume. (ref 19)
In another laboratory study, mice were induced with renal tumours; one group was fed shark cartilage and compared with control mice. (ref 20) The development of papillary and solid tumours was significantly delayed in the test group.
A randomised trial reported on the anti-angiogenic effects of shark cartilage in healthy volunteers. (ref 21) Twenty-nine male participants were divided into three groups and were given two daily doses of shark cartilage extract for 23 days. On day 12, a polyvinyl alcohol sponge threaded in perforated silicone tubing was inserted subcutaneously on the anterior side of the arm and removed on day 23. Endothelial cell density was measured as an indirect indicator of angiogenesis. The results indicated that the liquid cartilage extract reduced cell density. This trial was, however, not a clinical trial of cancer patients and the relevance of this finding for cancer is debatable. On the methodological quality scale the trial achieved 2 out of 5 points.
Uncontrolled trials
Several uncontrolled clinical studies have been published, which suggest anti-cancer effects of shark cartilage. Their results are clearly less conclusive than those from controlled clinical trials. One such trial reported that ten out of 20 cancer patients of different types experienced a partial or complete response after eight weeks of oral shark cartilage therapy. (ref 22)
Another uncontrolled trial included 144 patients with solid tumours who were given orally 60 or 240 ml Neovastat daily. A survival analysis of 22 of the patients suggested a significant dose-survival relationship. (ref 23)
In one Japanese study including 1,317 cancer patients, 3.0 to 6.0 g/day shark cartilage was administered over a three-month period and showed to have angiogenesis inhibitory effects. (ref 24) In another Japanese study, 184 patients with advanced colon cancer were given 20g/day oral shark cartilage, but no significant differences were found in the production of various cytokines. (ref 25)
An earlier study enrolled 20 patients with breast cancer and twelve patients with prostate cancer (ref 26) who were all treated with 1g/kg/day with an oral non-identified shark cartilage product. Another study included twelve patients with primary brain tumours who were given 96g/day in four divided doses of the commercially available product BeneFin. (ref 27) All patients had previously been treated with conventional therapy. No other anticancer treatment was allowed concurrently with cartilage therapy. Ten patients in each study completed at least eight weeks of treatment and were, therefore, 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 eight 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 2001, a phase II trial of AE-941/Neovastat was initiated in patients with relapsed or refractory multiple myeloma. (ref 28) This trial closed approximately one year later, however, and no results have been reported.
Finally, one phase I/II trial tested the safety and the efficacy of 1g/kg orally administered Cartilade in 60 patients with various types of advanced solid tumors in three divided dosages. (ref 29) 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 was given concurrently with Cartilade therapy. No complete responses or partial responses were observed among 50 evaluable patients who were treated for at least six weeks. However, stable disease that lasted twelve weeks or more was reported for ten of the 50 patients. All ten of these patients eventually experienced progressive disease.
To summarise the findings of the eight identified uncontrolled trials it can be said that patient sample size ranged from 12 to 1,317 patients, most of them suffering from various cancer types, some of them renal cell carcinoma patients 23, brain tumour patients (ref 27) or people with prostate and breast cancers (ref 26). Trial endpoints were mainly disease response (partial or complete), tumour progression, survival, angiogenesis inhibitory action, production of cytokines, quality of life and pain reduction. The results of these uncontrolled studies mainly showed no significant changes apart from a significant dose-survival relationship (ref 26) and a 50% increase in quality of life (ref 22).
Controlled trials
AE-941/Neovastat was also administered in a randomised phase III trial of BeneFin, of which 30 to 240 mL/day was administered to 331 patients with advanced solid tumours (including lung, prostate, breast, and kidney tumours). (ref 19) Patient recruitment ended in 2003 and they were randomly assigned to receive either cartilage or a placebo orally three to four times a day. Survival was the principal endpoint measured in this trial, but quality of life was also assessed. 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 suggests that AE-941/Neovastat is able to lengthen the survival of patients with this disease.
Two randomized phase III trials of AE-941/Neovastat in patients with advanced cancer have been approved by the United States Food and Drug Administration (FDA). In one trial, which is still ongoing, treatment with oral AE-941/Neovastat plus chemotherapy and radiation therapy is being compared to treatment with placebo, plus the same chemotherapy and radiation therapy, in patients with stage III non-small cell lung cancer. (ref 30) In the second trial, which closed to patient recruitment in 2002, treatment with oral AE-941/Neovastat was compared to 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 literature. The methodological quality of this trial cannot be assessed as the full results have not been published.
Finally, a recent RCT randomised 89 patients with advanced breast or colon cancer into two groups, to either receive an oral shark cartilage preparation three to four times daily or placebo. (ref 31) The results showed no significant differences between the two groups regarding survival rates and quality of life.
References
18. McGuire TR et al. Tamoxifen and shark cartilage: potential anti-angiogenic combination (Abstract from American College of Clinical Pharmacy Annual Meeting St. Louis, 1994). Pharmacotherapy 1994;14:362.
19. Falardeau P, Champagne P, Poyet P, et al. Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials. Semin Oncol 2001;28: 620-5.
20. Barber R, Delahunt B, Grebe SKG, Davis PF, Thornton A, Slim GC. Oral shark cartilage does not abolish carcinogenesis but delays tumor progression in a murine model. Anticancer Research 2001;21:1065-70.
21. Berbari P, Thibodeau A, Germanin L, Saint-Cyr M, Gaudreau P, Elkhouri S, Dupont E, Garrel DR, Elkouri S. Antiangiogenic effects of the oral administration of liquid cartilage extracts in humans. J Surg Res 1999;87:108-13.
22. Mathews J. Media feeds frenzy over shark cartilage as a cancer treatment. J Natl Cancer Inst 1993;85:1190-1191.
23. 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 2002;21:A-1907.
24. Yagita A. Role of angiogenesis inhibitor in novel immunotherapy for cancer (NITC). Biotherapy Japan 2000;14:973-82.
25. Maruyama S, Yagita A, Sukegawa Y, Daido A, Takeuchi S. Effect of a new immunotherapy for advanced colorectal cancer. Biotherapy Japan 2000;14:460-3.
26. 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 1998;17:A-240.
27. 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 1999;18:A-554.
28. Champagne P, Aeterna Laboratories, Incorporated Phase II Study of AE-941 (Neovastat) in Patients With Early Relapse or Refractory Multiple Myeloma, AETERNA-AE-MM-00-02, Clinical trial, Closed.
29. Miller DR. Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer. J Clin Oncol 1998;16:3649-3655.
30. Lu C, University of Texas - MD Anderson Cancer Center Phase III Randomized Study of Induction Platinum-Based Chemotherapy and Radiotherapy With or Without Æ-941 (Neovastat) in Patients With Unresectable Stage IIIA or IIIB Non-Small Cell Lung Cancer, MDA-ID-99303, Clinical trial, Active.
31. Loprinzi CL, Levitt R, Barton DL, Sloan JA, Atherton PJ, Smith DJ, Dakhil SR, Moore DF Jr, Krook JE, Rowland KM Jr, Mazurczak MA, Berg AR, Kim GP; North Central Cancer Treatment Group. Evaluation of shark cartilage in patients with advanced cancer – a north central cancer treatments group trial . Cancer 2005;104:176-82.
