BACKGROUND: Cisplatin reduces plasma ghrelin levels through the 5-hydroxytryptamine (5-HT) receptor. This may cause cisplatininduced gastrointestinal disorders and hinders the continuation of chemotherapy. The authors of this report conducted a prospective, randomized phase 2 trial to evaluate the effects of exogenous ghrelin during cisplatin-based chemotherapy. METHODS: Forty-two patients with esophageal cancer who were receiving cisplatin-based neoadjuvant chemotherapy were assigned to either a ghrelin group (n ¼ 21) or a placebo group (n ¼ 21). They received either intravenous infusions of synthetic human ghrelin (3 lg/kg) or saline twice daily for 1 week with cisplatin administration. The primary endpoint was changes in oral calorie intake, and the secondary endpoints were chemotherapy-related adverse events; appetite visual analog scale (VAS) scores; changes in gastrointestinal hormones and nutritional status, including rapid turnover proteins, and quality of life (QoL) estimated with the European Organization for Research and Treatment of Cancer QoL core questionnaire (QLQ-C30). RESULTS: Two patients were excluded from the final analysis: One patient suspended ghrelin administration because of excessive diaphoresis, and another patient in the placebo group failed to monitor the self-questionnaire. Food intake and appetite VAS scores were significantly higher in the ghrelin group than in the placebo group (18.2 AE 5.2 kcal/kg/day vs 12.7 AE 3.4 kcal/kg/day [P ¼ .001] and 6.2 AE 0.9 vs 4.1 AE 0.9 [P < .0001], respectively). Patients in the ghrelin group had fewer adverse events during chemotherapy related to anorexia and nausea than patients in the control group. Significant deterioration was noted after chemotherapy in the placebo group in QoL scores, appetite, nausea and vomiting, and global health status. CONCLUSIONS: Short-term administration of exogenous ghrelin at the start of cisplatin-based chemotherapy stimulated food intake and minimized adverse events. Cancer 2012;118:4785-94.

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Cisplatin-based chemotherapy significantly reduced plasma ghrelin and feeding activity. Ghrelin is a potentially useful novel therapy for minimizing the adverse effects of chemotherapy.

Background Gastric cancer patients who undergo gastrectomy suffer from a post-gastrectomy syndrome that includes weight loss, dumping syndrome, reflux esophagitis, alkaline gastritis, and finally malnutrition. It is important to ameliorate the post-gastrectomy symptoms to restore postoperative quality of life (QoL). The aim of this study was to investigate the effect of rikkunshito, a Japanese herbal medicine, on postoperative symptoms and ghrelin levels in gastric cancer patients after gastrectomy. Methods Twenty-five patients who had undergone gastrectomy received 2.5 g of rikkunshito before every meal for 4 weeks, and a drug withdrawal period was established for the next 4 weeks. Changes in gastrointestinal hormones, including ghrelin, and appetite visual analog scale scores were measured, and QoL was estimated by using the European Organization for Research and Treatment of Cancer core questionnaire QLQ-C30. The Dysfunction After Upper Gastrointestinal Surgery for Cancer (DAUGS) scoring system was used to evaluate gastrointestinal symptoms after gastrectomy. Results Sixteen men and nine women (mean age 61.9 years) were enrolled in the study. All patients had either stage I (n = 24) or II (n = 1) disease and had undergone either distal gastrectomy (n = 17) or total gastrectomy (n = 8) by a laparoscopy-assisted approach. The mean ratio of the acyl-/total ghrelin concentration increased significantly after rikkunshito administration (Pre: 7.8 ± 2.1, 4 weeks: 10.5 ± 1.7 %, p = 0.0026). The total DAUGS score, as well as the scores reflecting limited activity due to decreased food consumption, reflux symptoms, dumping symptoms, and nausea and vomiting significantly improved after rikkunshito administration. Conclusions The present study demonstrated a significant attenuation of gastrointestinal symptoms after gastrectomy by treatment with rikkunshito. Rikkunshito is potentially useful to minimize gastrointestinal symptoms after gastrectomy.

An early postoperative drop in plasma ghrelin correlated with prolonged SIRS after esophagectomy. Thus, the supplementation of low plasma ghrelin may help minimize excess inflammatory response in these patients.