title: Double-blind, placebo-controlled, randomized phase II study of TJ-14 (hangeshashinto) for gastric cancer chemotherapy-induced oral mucositis.
abstract: BACKGROUND
  Hangeshashinto (TJ-14, a Kampo medicine), which reduces the level of prostaglandin E2 and affects the cyclooxygenase activity, alleviates chemotherapy-induced oral mucositis (COM). We conducted a randomized comparative trial to investigate whether TJ-14 prevents and controls COM in patients with gastric cancer.
  
  
  METHODS
  We randomly assigned patients with gastric cancer who developed moderate-to-severe oral mucositis (CTCAE v4.0 grade ≧1) during any cycle of chemotherapy to receive either TJ-14 or a placebo as a double-blind trial. The patients received a placebo or TJ-14 for 2-6 weeks according to the chemotherapy regimen from the beginning of the next course of chemotherapy. The primary end point was the incidence of grade ≧2 oral mucositis in the protocol treatment course, and the secondary end points were the time to disappearance of oral mucositis and the incidence of adverse events.
  
  
  RESULTS
  Following the key opening of the blinding protocol, we analyzed 91 eligible patients (TJ-14: 45, placebo: 46) using a "per protocol set" analysis. The incidence of ≧grade 2 COM was 40.0 % in the TJ-14 group and 41.3 % in the placebo group (p = 0.588). The median duration of ≧grade 2 COM was 14 days in the TJ-14 group and 16 days in the placebo group (p = 0.894). Meanwhile, the median duration of any grade of COM was 9 days in the TJ-14 group and 17 days in the placebo group among the patients who developed grade 1 symptoms during the screening cycle [hazard ratio 0.60; 95 % CI (0.23-1.59), p = 0.290].
  
  
  CONCLUSIONS
  Although TJ-14 treatment did not reduce the incidence of ≥2 COM in the patients who developed mucositis during chemotherapy for gastric cancer, a trend was observed in which TJ-14 reduced the risk of COM in the patients who developed grade 1 COM during the screening cycle. Further, phase III studies with a larger sample size are needed to clarify the protective effects of TJ-14 for COM.
authors.affiliation: Department of Surgery, Miura City Hospital, Miura, Japan, aoyamat@kcch.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Aoyama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishikawa
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Takiguchi
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Tanabe
authors.forename: Motohiro
authors.initials: M
authors.lastname: Imano
authors.forename: Ryoji
authors.initials: R
authors.lastname: Fukushima
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.forename: Mari S
authors.initials: MS
authors.lastname: Oba
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Toru
authors.initials: T
authors.lastname: Kono
authors.forename: Akira
authors.initials: A
authors.lastname: Tsuburaya
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000150:complications* / Q000188:drug therapy; D013280:Stomatitis / Q000139:chemically induced* / Q000188:drug therapy / Q000209:etiology
chemical_list: D004365:Drugs, Chinese Herbal; C088236:hange-shashinto