Effects by daily long term provision of ghrelin to unselected weight-losing cancer patients: a randomized double-blind study.
BACKGROUND
The short-term provision of ghrelin to patients with cancer indicates that there may be benefits from long-term provision of ghrelin for the palliative treatment of weight-losing cancer patients. This hypothesis was evaluated in a randomized, double-blind, phase 2 study.


METHODS
Weight-losing cancer patients with solid gastrointestinal tumors were randomized to receive either high-dose ghrelin treatment (13 microg/kg daily; n = 17 patients) or low-dose ghrelin treatment (0.7 microg/kg daily; n = 14 patients) for 8 weeks as a once-daily, subcutaneous injections. Appetite was scored on a visual analog scale; and food intake, resting energy expenditure, and body composition (dual x-ray absorpitometry) were measured before the start of treatment and during follow-up. Serum levels of ghrelin, insulin, insulin-like growth factor 1, growth hormone (GH), triglycerides, free fatty acids, and glucose were measured. Health-related quality of life, anxiety, and depression were assessed by using standardized methods (the 36-item Short Form Health Survey and the Hospital Anxiety and Depression Scale). Physical activity, rest, and sleep were measured by using a multisensor body monitor.


RESULTS
Treatment groups were comparable at inclusion. Appetite scores were increased significantly by high-dose ghrelin analyzed both on an intent-to-treat basis and according to the protocol. High-dose ghrelin reduced the loss of whole body fat (P < .04) and serum GH (P < .05). There was a trend for high-dose ghrelin to improve energy balance (P < .07; per protocol). Otherwise, no statistically significant differences in outcome variables were observed between the high-dose and low-dose groups. Adverse effects were not observed by high-dose ghrelin, such as serum levels of tumor markers (cancer antigen 125 [CA 125], carcinoembryonic antigen, and CA 19-9).


CONCLUSIONS
The current results suggested that daily, long-term provision of ghrelin to weight-losing cancer patients with solid tumors supports host metabolism, improves appetite, and attenuates catabolism.
Lundholm
Kent
K
Department of Surgery, Surgical Metabolic Research Laboratory at Lundberg Laboratory for Cancer Research, Sahlgrenska Academy and University Hospital, Gothenburg, Sweden. kent.lundholm@surgery.gu.se
Gunnebo
Lena
L
Körner
Ulla
U
Iresjö
Britt-Marie
BM
Engström
Cecilia
C
Hyltander
Anders
A
Smedh
Ulrika
U
Bosaeus
Ingvar
I
D000368:Aged; D019167:Appetite Stimulants / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000150:complications*; D054439:Ghrelin / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009043:Motor Activity; D011788:Quality of Life; D015431:Weight Loss / Q000187:drug effects*
D019167:Appetite Stimulants; D054439:Ghrelin