Methylene Blue Mouthwash for Oral Mucositis Pain in Cancer: An Open-Label, Non-Randomized Study

Oral mucositis (OM) pain in patients undergoing cancer treatments remains inadequately managed with conventional treatments. This study aimed to examine pain outcomes associated with methylene blue (MB) mouthwash compared with a standard supportive care mouthrinse in hospitalized patients with OM.

In this open label, non-randomized clinical trial, patients selected MB (0.05%) or standard-of-care mixed medication mouthwash. Both groups performed an oral rinse every 8 h for three days. The primary outcome was change in pain numeric rating scores (0-10) from pre-administration to post-administration. Secondary outcomes included changes in daily oral intake volume and opioid use.

Forty-three evaluable patients were included in the analysis. Using a linear mixed model with subject-specific intercepts, both treatment groups demonstrated statistically significant reductions in pain from pre- to post- administration (standard of care: estimate=-0.64, 95% CI [-1.23, -0.05], p = 0.034; MB estimate=-0.87, 95% CI [-1.31, -0.42], p < 0.001). The administration timing-by-treatment interaction effect was not statistically significant, indicating that pain reduction did not differ significantly between groups.

In this non-randomized study, MB mouthwash was associated with short-term pain reductions in OM-related pain similar to standard-of-care mouthwash. These findings support feasibility and tolerability and underscore the need for larger randomized trials.