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: Toru Aoyama, Kazuhiro Nishikawa, Nobuhiro Takiguchi, Kazuaki Tanabe, Motohiro Imano, Ryoji Fukushima, Junichi Sakamoto, Mari S Oba, Satoshi Morita, Toru Kono, Akira Tsuburaya
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 73 Issue 5 Pg. 1047-54 (May 2014) ISSN: 1432-0843 [Electronic] Germany
• PMID: 24652604 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Drugs, Chinese Herbal
• hange-shashinto

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Double-Blind Method
• Drugs, Chinese Herbal (administration & dosage, adverse effects, therapeutic use)
• Female
• Humans
• Male
• Middle Aged
• Prospective Studies
• Stomach Neoplasms (complications, drug therapy)
• Stomatitis (chemically induced, drug therapy, etiology)