Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia/cachexia: a randomised, placebo-controlled, double blind, douple-crossover study

Twenty-one adult patients were randomized to receive ghrelin on days 1 and 8 and placebo on days 4 and 11, or vice versa, given intravenously over a 60– minute period before lunch: 10 received 2µg/kg (lower-dose) ghrelin; 11 received 8µg/kg (upper-dose) ghrelin. Active and total ghrelin, growth-hormone, and IGF-1 levels were monitored at baseline (4-5 days before day 1), during treatment days, and at end-of-study (day 17/18). Drug-related adverse events (assessed by NCI-CTC-toxicity criteria and cardiac examination), did not differ between ghrelin and placebo. No grade 3/4 toxicity or stimulation of tumor growth was observed. The peak increase of growth-hormone, a biological marker of ghrelin action, was 25ng/ml with lower-dose and 42ng/ml with upperdose ghrelin. Morning fasting total ghrelin levels were higher (p<0.05) for upperdose patients at end-of-study (3580pg/ml) than at baseline (990pg/ml). IGF-1 levels did not change. At day 8, 81% of patients preferred ghrelin over placebo and at the end-of-study, 63%. Nutritional intake and eating-related symptoms, measured to explore preliminary efficacy, did not differ between ghrelin and placebo. Ghrelin is well tolerated and safe in patients with advanced cancer. For safety, tolerance, and patients’ preference for treatment no difference was observed between the lower and upper-dose group.