Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia/cachexia: a randomised, placebo-controlled, double-blind, double-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.
Abstract
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.
TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.
Strasser, F