Phase I clinical study of fish oil fatty acid capsules for patients with cancer cachexia: Cancer and leukemia group B study 9473

The purpose of this study was to determine the maximum tolerated dose and d ose-limiting toxicities of fish oil fatty acid capsules containing omega-3 fatty acid ethyl esters. Twenty-two patients with neoplastic disease not am enable to curative therapy who had lost 2% of body weight over a previous 1 month time period were given an escalating dose of fish oh fatty acids. Th e maximum tolerated dose was found to be 0.3 g/kg per day of this preparati on. This means that a 70-kg patient can generally tolerate up to 21 1-g cap sules/day containing 13.1 g of eicosapentaenoic acid + docosahexaenoic acid , the two major omega-3 fatty acids. Dose-limiting toxicity was gastrointes tinal, mainly diarrhea, and a poorly described toxicity designated as "unab le to tolerate in esophagus or stomach." A patient with chronic lymphocytic leukemia taking the fish oil provided an unusual opportunity to perform a detailed biochemical study of the effect of fish oil capsules on the lipids of malignant cells at several sequential time points in treatment. Studies of the malignant lymphocytes, serum, and whole blood of this one patient r evealed an increase in eicosapentaenoic acid, the major component of the fi sh oil capsules, during fish oil capsule treatment. This study provides a s cientific basis for the selection of omega-3 fatty acid doses for future st udies in cancer. The maximum tolerated dose found is considerably higher th an anticipated from published studies of many human diseases. The observati on of a modification of the lipids of leukemic cells, serum, and blood in a patient with chronic leukemia provides a biochemical basis for a possible effect of fish oil supplements on cancer cachexia and tumor growth.