Shark Cartilage Fails to Benefit Lung Cancer Patients. Part 2
AE-941 is a standardized, water-soluble shark cartilage extract. The precise composition of the extract is not disclosed, but there is presumption that proteins in the extract are responsible for its activity. In vitro, it has been shown to induce endothelial cell apoptosis, inhibit matrix metalloproteinases, and inhibit vascular endothelial growth factor. Given orally in a mouse, it has demonstrated antimetastatic activity.
This favorable in vitro and in vivo data led to an open-label phase I–II dose escalation study assessing AE-941 (30, 60, 120, and 240 ml/d) in 80 patients with NSCLC. In this small trial there was a statistically significant improvement in survival in patients with Stage III/IV NSCLC (n=48) receiving the higher doses. Median survival time for the high-dose group was 6.1 months vs. 4.6 months in the low dose group (P=0.26).
The current phase III trial of NSCLC is much larger and better controlled than the pilot study. Although recruitment was stopped before the target sample size of 756 patients was met, the final sample size of 384 patients was adequate for statistical analysis. At years 1, 3, and 5, the overall survival rate in the AE-941 group was 59%, 25%, and 14% respectively. In the placebo group, the overall survival rates at 1, 3, and 5 years were 61%, 21%, and 14% respectively. No secondary endpoints resulted in statistical benefit either. This multicenter trial included both academic and community clinics and was well controlled and designed.
It is essential as practitioners that we stay apprised of new information on natural agents that are reputed to have anticancer effects. We should neither be swayed by the popular press nor be dismissive of ideas before all of the evidence is assessed. Shark cartilage is one example of a promising product in vitro that has just not proven itself in large clinical studies. While still sold on the market, there is insufficient evidence to warrant its use, and evidence provides direct refutation of its use in NSCLC. Of course, the supplement also takes an ecologic toll on the shark population, a separate but valid concern regarding its widespread use. The National Cancer Institute provides a comprehensive listing of all of the clinical trial data on the various shark cartilage products.
Limitations
AE-941 is a complex natural product, not a single agent. The company claims it is standardized, although there is no methodology or component breakdown to ensure replication or even consistency from batch to batch. The current study did not disclose batch numbers, so this is an unanswered question regarding the current study. The dose may not have been adequate, although the dose used in the study, 240 ml/d, was the highest level yet tested in a phase I study. The tolerable upper dose has not been set. Lastly, when given orally components in AE-941 may be broken down by digestion before reaching the bloodstream. Without any blood parameters of either ingredients or other blood markers to track, it is unclear whether AE-941 was adequately absorbed intact.