Shark Cartilage Does Not Improve Lung Cancer Survival: Phase III Results
Last Updated: 2010-05-26 17:08:00 -0400 (Reuters Health)
NEW YORK (Reuters Health) - The addition of the shark cartilage extract AE-941 (also known as Neovastat) to standard chemoradiotherapy does not improve survival in patients with inoperable stage III non-small-cell lung cancer (NSCLC), according to results of a large multicenter study published online May 26 in the Journal of the National Cancer Institute (JNCI).
The results were first reported at the American Society of Clinical Oncology's 2007 annual meeting. (See Reuters Health report June 4, 2007: Shark cartilage extract of no benefit in non-small cell lung cancer.)
The JNCI paper reports "the final results after all the data have been reviewed, and the overall results have not changed," Dr. Charles Lu, of The University of Texas M. D. Anderson Cancer Center, Houston, and the study's lead investigator told Reuters Health by phone.
"This compound clearly does not work," Dr. Lu said, "even though there was (antiangiogenic and antimetastatic) activity in animal models and preclinical studies and even though the Phase I and II trials were encouraging in the sense that folks who got the higher doses compared to the lower doses had a better outcome. I guess that must have been a fluke because we could not reproduce that."
Why did it take three years after presentation at ASCO for the results to be published? "JNCI was not the first place we submitted the data; we did try a couple others first and it went through review processes and got rejected, so that was a detour," Dr. Lu said. "Then at JNCI there was a fair amount of editorial back and forth and it took longer, actually, than I thought."
The Study - A Recap
The phase III study, which was sponsored by the National Cancer Institute and Aeterna Zentaris, the Canadian biopharmaceutical company that makes Neovastat, involved 384 patients with unresectable stage III NSCLC at 53 sites in the US and Canada.
Patients received standard induction chemotherapy followed by chemoradiotherapy and were randomly assigned to take Neovastat (120 mL p.o. twice daily) or placebo.
The final analysis was based on 379 patients -- 188 in the shark cartilage arm and 191 in the placebo arm.
After a median follow-up of 3.7 years and 283 observed deaths, there was no significant difference in overall survival between the Neovastat arm and the placebo arm. The median overall survival time was 14.4 months with Neovastat and 15.6 months without. The median time to progression was also not markedly different between the two arms (10.7 months with and 11.3 months without Neovastat). Nor was there any significant difference in progression-free survival.
The End of the Road?
In a written commentary, Dr. Jeffrey White, of the National Cancer Institute, Bethesda, Maryland, says questions will undoubtedly arise about generalizing the Neovastat results to other, or all, shark cartilage products, and perhaps to some or all complex natural products. "Some researchers may have the urge to say a larger question has been answered, thus completely disproving the efficacy of shark cartilage; however, as tempting as this may be, there are reasons to be more reserved in drawing such a conclusion," Dr. White says.
The study is missing some key information, he notes, including the process of standardization for Neovastat, "critical in research with complex natural products," data on compliance with treatment, the absence of a validated biomarker of antiangiogenic effect and, as the authors point out, their inability to do pharmacokinetic studies.
Moreover, Dr. White says the "slight, but statistically significant, decrease in grade 3 toxicities noted in the AE-941-treated group in the current study may be a sign of activity that is worthy of further investigation."
Purified components of shark cartilage are currently being studied and one or more of these "may hold therapeutic promise," he adds.
For now, he concludes, the "potential value of complex natural products in the anticancer armamentarium remains an open question for many and one that can only be answered one step at a time with high-quality research."
http://www.jnci.oxfordjournals.org
J Natl Cancer Inst 2010.
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