PHASE I II TRIAL OF THE SAFETY AND EFFICACY OF SHARK CARTILAGE IN THETREATMENT OF ADVANCED CANCER/

Purpose: Patients with cancer and chronic inflammatory disorders have used shark cartilage (SC) preparations for many years. preclinical stu dies that support their beneficial effects are scanty, and reports of clinical trials have been anecdotal. The proposed mechanisms of antitu mor action include direct or indirect inhibition of angiogenesis. Beca use of the emerging use of SC as an alternative to conventional cancer therapy this trial was launched to evaluate the safety and efficacy o f SC. patients and Methods: Sixty adult patients with advanced previou sly treated cancer (breast, 16 patients; colorectal, 16 patients; lung , 14 patients; prostate, eight patients; non-Hodgkin lymphoma, three p atients; brain, one patient; and unknown primary tumor, two patients) were enrolled, Eligibility criteria included confirmation of diagnosis , resistance to conventional therapy, objective measurable disease, li fe expectancy of 12 weeks or greater, Eastern Cooperative Oncology Gro up (ECOG) performance status of 0 to 2, no recent or concomitant antic ancer therapy, no prior SC, and informed consent. Patients underwent e valuation 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 aft er 6 and 12 weeks of SC therapy. The dose of SC was 1 g/kg daily orall y in three divided doses, Standard criteria were used to evaluate adve rse events and response. Results: Ten of 60 patients were lost to foll ow-up(LTFU) or refused further treatment (RFT) before the 6-week evalu ation and were not assessable for toxicity and response. Three patient s with stable disease at 6 weeks were LTFU or RFT thereafter. Of the 4 7 fury assessable patients, five were taken off study because of gastr ointestinal toxicity or intolerance to SC. Progressive disease (PD) at 6 or 12 weeks occurred in 22 and five patients, respectively. Five pa tients died of PD while undergoing SC therapy. No complete (CRs) or pa rtial responses (PRs) were noted. Median time to tumor progression in the entire study population was 7 +/- 9.7 weeks (mean, 11.4 weeks; ran ge, 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 wee ks or more. The median time to tumor progression was 27 weeks, the mea n was 28.8 +/- 9.9 weeks, and the range was 18.6 to 45.7 weeks, In thi s subset, FACT-G scores improved in four patients, were unchanged in f our 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 can cer and had no salutary effect on qualify of life. The 16.7% rate of S D was similar to results in patients with advanced cancer treated with supportive care alone. (C) 1998 by American Society of Clinical Oncol ogy.