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

• Published in: British journal of cancer Vol. 98; no. 2; pp. 300 - 308
• Main Authors: Strasser, F, Lutz, T A, Maeder, M T, Thuerlimann, B, Bueche, D, Tschöp, M, Kaufmann, K, Holst, B, Brändle, M, von Moos, R, Demmer, R, Cerny, T
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.01.2008; Nature Publishing Group
• Subjects: Aged; Aged, 80 and over; Algorithms; Anorexia; Anorexia - drug therapy; Anorexia - etiology; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cachexia - drug therapy; Cachexia - etiology; Cancer Research; Cancer therapies; Clinical Study; Colorectal cancer; Cross-Over Studies; Double-Blind Method; Drug dosages; Drug Resistance; Epidemiology; Female; Ghrelin - administration & dosage; Ghrelin - adverse effects; Ghrelin - pharmacokinetics; Growth hormones; Hematology; Humans; Infusions, Intravenous; Insulin-like growth factors; Internal medicine; Male; Medical research; Medical sciences; Medicine; Middle Aged; Molecular Medicine; Neoplasms - complications; Oncology; Palliative care; Pharmacokinetics; Physiology; Placebos; Toxicity; Tumors; Switzerland; ghrelin; nutrition; anorexia; cachexia; Anorexia; Intravenous administration; Nutrition; Cachexia; Malignant tumor; Feeding; Randomization; Cancerology; Diet; Placebo; Double blind study; Pharmacokinetics; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6604148

Twenty-one adult patients were randomised to receive ghrelin on days 1 and 8 and placebo on days 4 and 11 or vice versa, given intravenously over a 60-min period before lunch: 10 received 2  μ g kg −1 (lower-dose) ghrelin; 11 received 8  μ g kg −1 (upper-dose) ghrelin. Active and total ghrelin, growth hormone (GH), and insulin-like growth factor 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 tumour growth was observed. The peak increase of GH, a biological marker of ghrelin action, was 25 ng ml −1 with lower-dose and 42 ng ml −1 with upper-dose ghrelin. Morning fasting total ghrelin levels were higher ( P <0.05) for upper-dose patients at end of study (3580 pg ml −1 ) than at baseline (990 pg ml −1 ). Insulin-like growth factor 1 levels did not change. At day 8, 81% of patients preferred ghrelin to placebo as against 63% at the end of study. 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.