The absence of blood vessels in cartilage as well as preclinical studies analyzing cartilage extracts have supported the hypothesis that cartilage contains inhibitors of angiogenesis. Also, shark cartilage has long intrigued the public due to the belief that the incidence of cancer in this cartilaginous fish is very rare. Early Phase I and II studies in lung and renal cancers suggested some benefit to patients when AE-941 was given at higher doses, said Charles Lu, M.D. associate professor in MD Anderson’s Department of Thoracic Head and Neck Medical Oncology.
“This is the first large Phase III randomized trial of shark cartilage as a cancer agent. A unique and important aspect about this shark cartilage study was that this product, Neovastat, was never sold over-the-counter, unlike other shark cartilage compounds previously studied. The company, Aeterna Zentaris, developed the compound as a pharmaceutical as opposed to a compound sold for profit that is available over the Internet, for example,” said Lu, the study’s national principal investigator and corresponding author.
The international Phase III study enrolled 379 newly-diagnosed untreated Stage III non-small cell lung cancer patients at 53 sites in the United Sates and in Canada from June 2000 to February 2006. MD Anderson enrolled 60 patients in the trial.
The study was initiated at the request of, and was supported by, the National Cancer Institute (NCI) who sought proposals from pharmaceutical companies regarding their shark cartilage agents.
All study participants received the standard treatment of induction chemotherapy and chemo-radiation. Patients were randomized to receive either shark cartilage or placebo, both in the form of a liquid. Patients drank four ounces of the extract twice daily, and continued on the shark cartilage/placebo as maintenance after completing standard therapy.
Researchers say that the study did not meet its primary endpoint: survival. With a median follow-up of 3.7 years, researchers did not find a statistical difference in survival between patients who received the shark cartilage, 14.4 months, and those who received the placebo, 15.6 months.
“Clearly, these results demonstrate that AE-941 is not an effective therapeutic agent for lung cancer,” said Lu. “So, too, these findings have to cast major skepticism on shark cartilage products that are being sold for profit and have no data to support their efficacy as cancer-fighting agent.”
Patients who are currently taking shark cartilage should be very cautious in accepting that the therapy will be beneficial, warns Lu.
“We have absolutely no data showing improvements in survival, tumor shrinkage and/or clinical benefits to patients,” said Lu. “Now when patients ask their oncologists about shark cartilage, physicians can point to this large NCI-sponsored Phase III trial and tell patients that, at this point, the only studies that have been done with cartilage-derived products have been negative.”
Lung cancer is the leading cancer killer in both men and women; according to the American Cancer Society, approximately 219,440 were diagnosed with lung cancer – in 2009 and 159,390 died from the disease.
Non-small cell is the most common type of the disease, accounting for about 80% of all lung cancers, said Lu.
Aeterna Zentaris, a biopharmaceutical company based in Quebec, Canada, stopped clinical development the compound. Both the NCI and Aeterna Zentaris supported the study.
In addition to Lu, other authors on the study include: Ritsuko Komaki, M.D., Department of Radiation Oncology, Roy Herbst, M.D., Ph.D., Department of Thoracic Head and Neck Medical Oncology, Mylene Truong, MD. Department of Diagnostic Radiology, J. Jack Lee, Ph.D. and Lei Feng, both of the Department of Biostatistics, Michael Fisch, M.D., Department of General Oncology, all from MD Anderson; Archie Bleyer, M.D., Oregon Health and Science University; William K. Evans, M.D. Juravinski Cancer Centre; Hak Choy, M.D., The University of Texas Southwestern Medical Center, Pierre Desjardins, M.D. Hopital Charles Lemoyne; Benjamin T. Esparaz, M.D., Decatur Memorial Hospital; Scott Saxman, M.D., Cancer Therapy Evaluation Program; Joseph Kelaghan, MD., National Cancer Institute. 05/26/10