Topical Application of TJ-14 (Hangeshashinto) in the Treatment of Chemotherapy-Induced Oral Mucositis: A Radomized, Placebo-Controlled, Double-Blind, Phase II Trial

ABSTRACT Background and aims Although chemotherapy-induced oral mucositis (COM) is a common side effect of many anticancer therapies, the optimal treatment for this condition is not well established. Recent studies showed that one of the traditional Japanese herbal medicines (Kampo) called TJ-14 (hangeshashinto) may be useful for COM via downregulating pro-inflammatory prostaglandins in the cyclooxygenase pathway (ASCO-GI2011, AGA2012). The efficacy of TJ-14 for the prevention and/or treatment of COM was exploratively tested in a randomized, double-blind, placebo-controlled trial in colorectal cancer patients. Methods Ninety-three patients who developed COM during FOLFOX, FOLFIRI or XELOX treatment for advanced colorectal cancer were centrally randomized to receive either a topical application of TJ-14 or placebo. Patients were advised to dissolve 2.5 g of TJ-14 or placebo in 50 mL of tap water and rinse their oral cavity three times daily for 10 seconds with the solution before expectorating it. Patients followed this oral care throughout the treatment before the next course of chemotherapy began. The COM grade was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 4 and a self-administered questionnaire before and after the 2-week treatment with the TJ-14 or placebo solution. The study endpoints included the incidence of worst grade COM, the incidence of grade 2 or higher COM, the duration of grade 2 or higher COM, and the healing time of COM. Results Ninety patients (43 in the TJ-14 group, 47 in the placebo group) were included in the statistical analysis. The incidence of grade 3 COM was 9.5% vs. 17%, while no significant difference in the incidence of grade 2 or higher COM was found between the two groups. The median duration of grade 2 or higher COM was 5.5 days vs. 10.5 days (p = 0.018). No significant difference was observed between the two groups with regard to the incidence of grade 2 or higher adverse events. Conclusions Topical TJ-14 rinse appears to have a significant ability to treat grade 2 or higher COM and reduce the risk of developing grade 3 COM. Our results are encouraging and warrant further phase III trials. Disclosure All authors have declared no conflicts of interest.