Background
Natural ghrelin, a peptide growth hormone secretagogue, has a therapeutic potential in cachexia. We designed a dose-finding trial of subcutaneous natural ghrelin to improve nutritional intake (NI) in advanced cancer patients.
Conclusions
Ghrelin was safe in advanced patients with cancer cachexia without dose-limiting toxicity and well tolerated. The intervention was very complex, and the number of patients included was small. There was a positive effect on nutritional intake and patient narratives.
Methods
Advanced cancer patients with cachexia management (symptom management, physiotherapy, nutritional, and psychosocial support) started with ghrelin at 32 μg/kg body weight, followed by 50% dose increases. Patients self-injected ghrelin twice daily for 4 days followed by a wash-out period. After reaching the primary endpoint, maximal NI (minimal dose for maximal NI), a maintenance period followed during which patients injected 10 doses of ghrelin per week. Safety parameters, NI, and cachexia outcomes (symptoms, narratives, muscle mass, and strength) were measured over 6 weeks.
Results
Ten patients with metastatic solid tumours were included, and six (100% male, mean age 61.8 ± 8.5 SD) received ghrelin. Minimal dose for maximal NI was reached in four patients. Three patients reached the end-of study visit. Ghrelin was well tolerated with variable results on appetite and eating-related symptoms but a positive effect in the narratives. Mean Functional Assessment of Appetite & Cachexia Therapy score was 6.8 points lower at final measurement compared with baseline, t(5) = 5.98, P < .01. Muscle mass was stable in two patients and increased in one patient, and muscle strength was stable in three patients. Subjective tolerability was high. Patients showed a fluctuating trajectory, and median survival was 88 days (51-412 days). Conclusions: Ghrelin was safe in advanced patients with cancer cachexia without dose-limiting toxicity and well tolerated. The intervention was very complex, and the number of patients included was small. There was a positive effect on nutritional intake and patient narratives.