Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer

PURPOSE: Patients with cancer and chronic inflammatory disorders have used shark cartilage (SC) preparations for many years. Preclinical studies that support their beneficial effects are scanty, and reports of clinical trials have been anecdotal. The proposed mechanisms of antitumor action include direct or indirect inhibition of angiogenesis. Because of the emerging use of SC as an alternative to conventional cancer therapy, this trial was launched to evaluate the safety and efficacy of SC. PATIENTS AND METHODS: Sixty adult patients with advanced previously treated cancer (breast, 16 patients; colorectal, 16 patients; lung, 14 patients; prostate, eight patients; non-Hodgkin lymphoma, three patients; brain, one patient; and unknown primary tumor, two patients) were enrolled. Eligibility criteria included confirmation of diagnosis, resistance to conventional therapy, objective measurable disease, life expectancy of 12 weeks or greater, Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, no recent or concomitant anticancer therapy, no prior SC, and informed consent. Patients underwent evaluation of the extent of disease, quality-of-life score (Functional Assessment of Cancer Therapy-General [FACT-G] scale), and hematologic, biochemical, and selected immune function studies at baseline and after 6 and 12 weeks of SC therapy. The dose of SC was 1 g/kg daily orally in three divided doses. Standard criteria were used to evaluate adverse events and response. RESULTS: Ten of 60 patients were lost to follow-up(LTFU) or refused further treatment (RFT) before the 6-week evaluation and were not assessable for toxicity and response. Three patients with stable disease at 6 weeks were LTFU or RFT thereafter. Of the 47 fully assessable patients, five were taken off study because of gastrointestinal toxicity or intolerance to SC. Progressive disease (PD) at 6 or 12 weeks occurred in 22 and five patients, respectively. Five patients died of PD while undergoing SC therapy. No complete (CRs) or partial responses (PRs) were noted. Median time to tumor progression in the entire study population was 7+/-9.7 weeks (mean, 11.4 weeks; range, 3.7 to 45.7 weeks). Ten (20%) of 50 assessable patients, or 16.7% of the 60 intent-to-treat patients, had stable disease (SD) for 12 weeks or more. The median time to tumor progression was 27 weeks, the mean was 28.8+/-9.9 weeks, and the range was 18.6 to 45.7 weeks. In this subset, FACT-G scores improved in four patients, were unchanged in four patients, and declined in two patients. Twenty-one adverse events (grade 1, eight events; grade 2, seven events; and grade 3, six events) were recorded, 14 of which were gastroenterologic (nausea, vomiting, constipation). CONCLUSION: Under the specific conditions of this study, SC as a single agent was inactive in patients with advanced-stage cancer and had no salutary effect on quality of life. The 16.7% rate of SD was similar to results in patients with advanced cancer treated with supportive care alone.