Ghrelin is a hormone produced mainly in the stomach and is responsible for stimulating appetite and attenuating mucosal damage caused by cytotoxic agents. Digestive symptoms such as appetite loss frequently occur in patients with pancreatic cancer (PC) who are undergoing chemotherapy and may be influenced by ghrelin. The aim of this study was to elucidate the role of plasma ghrelin levels in digestive symptoms among patients with advanced PC.Methods
Patients with treatment-naïve advanced PC and no infectious conditions were eligible. All the patients were scheduled to undergo chemotherapy. Symptoms were rated numerically from 0 (not present) to 10 (as bad as you can imagine) using the Japanese version of the MD Anderson Symptom Inventory. Adverse events were evaluated according to the CTCAE, v3.0. The plasma des-acyl ghrelin (D-ghrelin) level was measured by N.M. and M.N. The measurements were carried out before chemotherapy and one month later. A two-tailed paired Student's t-test was used to compare repeated measurements.Results
Eighty-seven patients (female/male: 40/47, median age: 65 years, Karnofsky performance status [KPS] of 100–90/80–70/60: 61/25/1, liver metastasis absent/present: 44/43) were studied. All the patients received chemotherapy (gemcitabine [GEM]/GEM-based/S-1: 47/24/16). The D-ghrelin level before chemotherapy (mean, 58.1 ± 5.4 fmol/ml) was lower than that observed 1 month later (mean, 68.0 ± 6.0 fmol/ml; P < 0.001). A high D-ghrelin level was defined as a value greater than the mean value observed before chemotherapy. Patients were divided into high (n = 43) or low (n = 44) D-ghrelin groups according to their D-ghrelin level before chemotherapy. A poor KPS before chemotherapy, defined as a KPS score of <80, was frequently observed in the high D-ghrelin group (39.5%), compared with the low D-ghrelin group (18.2%, P = 0.034). When the repeated symptom scores for 1 month were compared, nausea and vomiting had worsened in the high D-ghrelin group (P = 0.002 and P = 0.001). A tendency toward a worsening of appetite loss after one month was observed in the high D-ghrelin group (P = 0.054).Conclusion
A high plasma D-ghrelin level was related to a poor KPS and a worsening of nausea and vomiting in patients with advanced PC who received chemotherapy.