Natural ghrelin in advanced cancer patients with cachexia, a case series

Abstract

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. 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.

Cancer Cachexia: Its Mechanism and Clinical Significance

“…Ghrelin not only promotes appetite, but also has anti-inflammatory effects, inhibits muscle protein degradation via MuRF-1/MAFbx, promotes muscle protein synthesis via IGF-1, inhibits apoptosis, increases fat storage, and decreases energy expenditure, and is thought to ameliorate multiple pathologies of cancer cachexia [63]. In a study of a small number of patients, natural ghlerin administration to patients with advanced cancer was reported to be well tolerated and improve nutritional status [64]. Leptin, secreted by adipose tissues, is an anti-obesity hormone that suppresses appetite by acting on leptin receptors in the hypothalamus [65].…”

Managing Cachexia in Head and Neck Cancer: a Systematic Scoping Review

“…After deleting duplicates (N = 580), irrelevant papers (N = 1357), and exclusions (N = 32), we found nine studies eligible to be included in this scoping review as shown in Fig. 1 [23][24][25][26][27][28][29][30][31].…”

“…Of the nine included studies, five (55.6%) had been carried out in Europe [23,25,26,28,31] and two (22.2%) studies each in the US [24,30] and Asia [27,29]. From the included studies, two (22.2%) recommended both nutritional and pharmacologic interventions for the management of cachexia in HNC patients [23,25].…”

“…From the included studies, two (22.2%) recommended both nutritional and pharmacologic interventions for the management of cachexia in HNC patients [23,25]. Three (33.3%) studies each suggested only either nutritional intervention [27,30,31] or pharmacologic intervention [24,26,29]. Similarly, only one study (14.3%) suggested other emerging interventions in addition to the nutritional and pharmacologic interventions such as exercise or resistance training [28].…”

Protective and Healing Effects of Ghrelin and Risk of Cancer in the Digestive System

“…There are clinical observations indicating that ghrelin and anamorelin are an effective pharmacotherapeutic option for patients with advanced malignancies and cancer cachexia. The study carried out by Blum et al [ 269 ] have shown that natural ghrelin given subcutaneously in advanced cancer patients with cachexia, is safe and well-tolerated without dose-limiting toxicity. In patients’ opinion, treatment with ghrelin increased their appetite and reduced the negative symptoms associated with food intake.…”