Yamashita, T., Araki, K., Tomifuji, M., Kamide, D., Tanaka, Y., & Shiotani, A. (2014). A traditional Japanese medicine-Hangeshashinto (TJ-14)-alleviates chemoradiation-induced mucositis and improves rates of treatment completion. Supportive Care in Cancer, 23, 29–35. 

To investigate the efficacy of a traditional Japanese medicine, hangeshashinto (TJ-14), in the prevention of chemoradiation-induced oral mucositis

Records were reviewed retrospectively. All patients underwent fractioned radiation with or without concurrent chemotherapy. Researchers compared data from 40 patients who were treated with TJ-14 to those of 40 patients who underwent radiotherapy or concurrent chemoradiotherapy treatment during the study period and did not receive TJ-14 (the control group). Those who received TJ-14 rinsed and gargled with 2.5 g of the intervention drug dissolved in 100 mL of oral rinse solution. Patients rinsed and gargled with the solution three times per day for 30 seconds after meals and during and after chemoradiation treatment and then swallowed or expectorated the solution. No food or drink was allowed for 30 minutes after treatment. Both groups brushed and gargled with six drops of 4% sodium gualenate hydrate and tap water as well as lidocaine gargle, NSAIDs, and opioids as needed.

• N = 80  
• AVERAGE AGE = 68 years
• MALES: 95%, FEMALES: 5% 
• KEY SAMPLE CHARACTERISTICS: Patients who underwent whole-neck radiation of > 60 Gy with or without chemotherapy

• SITE: Single-site
• SETTING TYPE: Outpatient  
• LOCATION: Japan

• PHASE OF CARE: Active treatment

Retrospective chart review comparing those who used the study medication and those who did not.

• National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4 for oral mucositis

A mulivariate analysis indicated that the use of TJ-14 (p = .019), a patient's gender (p = .024), and a patient's primary tumor location (p = .028) were significant factors associated with the severity of oral mucositis. TJ-14 was associated with a significantly improved rate of completion of chemoradiation with cisplatin (p = .002). However, the study purpose was to prove the effectiveness in preventing oral mucositis. No primary endpoint was ever mentioned.

Additional studies to determine effectiveness are needed. Future studies should be more specific as to the type of chemotherapy used and how by whom oral assessments are completed. The authors of this study were trying to measure too many variables within one small study. Study purpose was too general.

• Small sample (< 100)
• Baseline sample/group differences of import
• Risk of bias (no random assignment)
• Key sample group differences that could influence results 
• Measurement/methods not well described 
• Measurement validity/reliability questionable 
• Findings not generalizable
• Other limitations/explanation: No way to validate whether the oral assessments were reliable, valid, or reproducible. The measurement method was questionable. The written report was confusing and contained too many study variables.

This retrospective record review provides a platform on which well-designed, randomized, controlled studies can be based to evaluate the effectiveness of TJ-14 for the prevention of oral mucositis. Well-designed studies are needed to prove the effectiveness of this medication.