Shark Cartilage Fails to Benefit Lung Cancer Patients
Design
Multicenter, randomized, double-blinded, placebo-controlled phase III trial. Three hundred seventy-nine patients with unresectable stage III non-small cell lung cancer (NSCLC) were enrolled between June 5, 2000, and February 6, 2006. All patients received chemotherapy, including a platinum-based agent, and radiotherapy. Patients were randomly assigned in a 1:1 ratio to receive either 120 ml of AE-941 (Neovastat) (n=188) or an equal dose of placebo (n=191) orally twice daily. The groups were stratified for stage (IIIA or IIIB), chemotherapy regimen, and gender. Assessment of tumor status with computed tomography (CT) was made at baseline, before thoracic radiotherapy (which began day 50), and at 6 weeks post radiotherapy. The primary endpoint was overall survival. Secondary endpoints included time to progression (TTP), progression-free survival (PFS), tumor response rate, and toxic effects.
Key Findings
There was no statistically significant difference in overall survival in those taking AE-941 versus placebo: 14.4 months (95% CI=12.6–17.9 months) vs. 15.6 months (95% CI=13.8–18.1 months). There was also no statistically significant difference between the AE-941 and placebo groups in any of the the secondary endpoints of the trial. Median TTP=11.3 months (95% CI =9.0–16.8 months) in AE-941 vs. 10.7 months (95% CI=9.5–21.6 months) in the placebo group. Similar results were obtained for progression-free survival.
Practice Implications
The use of shark cartilage as an alternative cancer treatment has been touted in lay media for many years. In 1992 William Lane published Sharks Don’t Get Cancer: How Shark Cartilage Could Save Your Life, which coincided with a product he sold, shark cartilage extract (Benefin). The use of shark cartilage is an interesting story of the best and worst in the marketing and development of natural agents. While a product was being sold on the market, much of the scientific community dismissed its use out of hand based on hyperbole and lack of evidence. Meanwhile, there was diligent pursuit of evidence of its anticancer activity by the Canadian pharmaceutical company Aeterna Zentaris, owners of AE-941 (Neovastat).
Up until 2003, AE-941 appeared to be a legitimately promising agent, with data accumulating on its anticancer effects both in vitro and in vivo. This included a 2002 study of advanced cancers that showed a cohort of renal cell cancer patients (n=22) had improved survival in the high-dose (240 ml/d) group compared with the low-dose (60 ml/d) group (16.3 vs. 7.1 months). However, a phase III study presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in 2003 reported there was no benefit to overall survival when used as a sole agent in patients with kidney cancer refractory to immunotherapy.
The current study, which is much larger and better controlled than any previously published trials, now provides sufficient evidence to refute the use of shark cartilage in patients with NSCLC, and to dampen any enthusiasm of its use as an anticancer agent in general.