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 dose-limiting toxicities of fish oil fatty acid capsules containing omega-3 fatty acid ethyl esters. Twenty-two patients with neoplastic disease not amenable to curative therapy who had lost 2% of body weight over a previous 1 month time period were given an escalating dose of fish oil fatty acids. The maximum tolerated dose was found to be 0.3 g/kg per day of this preparation. This means that a 70-kg patient can generally tolerate up to 21 1-g capsules/day containing 13.1 g of eicosapentaenoic acid + docosahexaenoic acid, the two major omega-3 fatty acids. Dose-limiting toxicity was gastrointestinal, mainly diarrhea, and a poorly described toxicity designated as "unable 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 revealed an increase in eicosapentaenoic acid, the major component of the fish oil capsules, during fish oil capsule treatment. This study provides a scientific basis for the selection of omega-3 fatty acid doses for future studies in cancer. The maximum tolerated dose found is considerably higher than anticipated from published studies of many human diseases. The observation 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.

Limited impact of total parenteral nutrition on nutritional status during treatment for small cell lung cancer.

During a randomized trial of total parenteral nutrition (TPN) in patients with small cell lung cancer, we evaluated the short- and long-term effects of 4 weeks of TPN on nutritional assessment parameters. All 119 patients who were accrued to the study received the same chemotherapy and radiotherapy protocol which extended over a 1-year period: 57 patients received TPN; and 62 served as controls. At base line, patients with greater than 5% pretreatment weight loss had significantly lower levels of serum albumin, total iron-binding capacity, and creatinine/height index. TPN administration led to a significant increase in mean caloric intake and weight compared with controls (P less than 0.0001). In the short-term study, body fat, as measured by triceps skinfold thickness, was maintained, and there was a small increase in arm muscle circumference. Serum albumin and hematocrit decreased but promptly returned to pretreatment levels when TPN was stopped. There were no long-term differences in any of the nutritional assessment parameters between the two groups.

Effect of adjuvant central iv hyperalimentation on the survival and response to treatment of patients with small cell lung cancer: a randomized trial.

The effect of central iv hyperalimentation (IVH) as an adjunct to aggressive antineoplastic therapy for small cell carcinoma of the lung was evaluated in a randomized trial with 119 evaluable patients. IVH was given over a 28-day period with higher caloric and protein intake for patients nutritionally depleted on entry in the study; all patients were escalated in caloric and protein intake to maximize nutritional repletion. Combination chemotherapy and radiation therapy induced a 45.5% complete response rate and an overall response rate of 92.8%. Median survival for patients with limited disease was 18 months; median survival for patients with extensive disease was 11 months. Patients randomized to receive IVH did not have a better response rate (P = 0.97) or survival (P = 0.78) than control patients. IVH did not significantly alter the survival for patients who at baseline had greater than 5% pretreatment weight loss, low caloric intake, decreased serum albumin, or reduced total iron-binding capacity. Significantly more febrile episodes were seen in IVH patients than in control patients (P less than 0.001). Short-term IVH to patients with this malignancy who are capable of enteral alimentation cannot be routinely recommended as adjunctive therapy.