Total gastrectomy-induced reductions in food intake and weight are counteracted by rikkunshito by attenuating glucagon-like peptide-1 elevation in rats.

BACKGROUND: Decrease in appetite and weight after total gastrectomy in patients with gastric cancer leads to a decrease in quality of life, increased mortality, and may necessitate discontinuation of adjuvant chemotherapy. The aim of this study is to determine whether rikkunshito, a Japanese herbal medicine, increases food intake and weight after gastrectomy in rats. METHODS: Male rats underwent gastrectomy followed by roux-en-Y reconstruction or sham operation and were then treated with rikkunshito for 14 days starting on postoperative day 3. Daily food intake, weight, plasma glucagon-like peptide-1 (GLP-1), and ghrelin levels were measured. A pilot study to measure pre- and postoperative plasma GLP-1 levels was conducted in patients who underwent total gastrectomy for gastric cancer. RESULTS: Administration of rikkunshito after gastrectomy in rats significantly increased food intake and weight, which continued for at least 2 weeks after treatment. Both fasting and postprandial plasma GLP-1 levels were increased markedly after gastrectomy compared with sham-operated animals. Increased GLP-1 levels in rats after gastrectomy were suppressed markedly by rikkunshito. rikkunshito had no significant effect on plasma ghrelin levels after gastrectomy. Treatment with a GLP-1 receptor antagonist significantly improved food intake and weight after gastrectomy. Plasma fasting GLP-1 levels in patients with gastric cancer were increased greatly after gastrectomy on postoperative day 1. CONCLUSION: Administration of rikkunshito suppresses plasma GLP-1 levels after total gastrectomy, which is associated with recovery from reduced food intake and weight in rats.

Phase II feasibility study of preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for esophageal squamous cell carcinoma.

The combination of docetaxel, cisplatin, and 5-fluorouracil (DCF) as preoperative treatment for esophageal squamous cell carcinoma (ESCC) has not been investigated. We carried out a multicenter phase II feasibility study of preoperative chemotherapy with DCF for ESCC. Patients with clinical stage II/III ESCC (International Union Against Cancer TNM classification system, 6th edition) were eligible. Chemotherapy consisted of i.v. docetaxel (70-75 mg/m(2)) and cisplatin (70-75 mg/m(2)) on day 1, and continuous infusion of fluorouracil (750 mg/m(2)/day) on days 1-5. Antibiotic prophylaxis on days 5-15 was mandatory. This regimen was repeated every 3 weeks with a maximum of three cycles allowed. After completion of chemotherapy, esophagectomy with extended lymphadenectomy was carried out. The primary endpoint was the completion rate of protocol treatment. Forty-two eligible patients were enrolled. During chemotherapy, the most common grade 3 or 4 toxicities were neutropenia (83%), anorexia (7%), and stomatitis (5%). Forty-one (98%) patients underwent surgery. The completion rate of protocol treatment was 90.5% (38/42). No treatment-related death was observed and the incidence of operative morbidity was tolerable. According to RECIST, the overall response rate after the completion of DCF was 64.3%. Pathological complete response was achieved in 17%. The estimated 2-year progression-free survival and overall survival were 74.5% and 88.0%, respectively. Although these data are preliminary, preoperative DCF was well tolerated. Antitumor activity was highly promising and warrants further investigation. This trial was registered with University Hospital Medical Information Network (no. UMIN000002396).