Methylene blue for intractable pain from oral mucositis related to cancer treatment: a randomized phase 2 clinical trial

Abstract

Background Oral mucositis (OM) in patients receiving cancer therapy is thus far not well managed with standard approaches. We aimed to assess the safety and effectiveness of methylene blue (MB) oral rinse for OM pain in patients receiving cancer therapy. Methods In this randomized, single-blind phase 2 clinical trial, patients were randomized to one of four arms: MB 0.025%+conventional therapy (CTx) (n = 15), MB 0.05%+CTx (n = 14), MB 0.1%+CTx (n = 15), or CTx alone (n = 16). Intervention groups received MB oral rinse every 6 h for 2 days with outcomes measured at days 1–2; safety was evaluated up to 30 days. The primary outcome measured change in the pain numeric rating scale (0–10) from baseline to day 2. Secondary outcome measured change in oral function burden scores from baseline to day 2, World Health Organization OM grades, morphine equivalent daily doses, and adverse events. The trial was registered with ClinicalTrials.gov ID: NCT03469284. Results Sixty patients (mean age 43, range 22–62 years) completed the study. Compared with those who received CTx alone, those who received MB had a significant reduction of pain scores at day 2 of treatment (mean ± SD); 0.025%: 5.2 ± 2.9, 0.05%: 4.5 ± 2.9, 0.1%: 5.15 ± 2.6) and reduction of oral function burden scores (0.025%: 2.5 ± 1.55, 0.05%: 2.8 ± 1.7, 0.1%: 2.9 ± 1.60). No serious adverse events were noted, but eight patients reported burning sensation of the oral cavity with the first dose, and this caused one patient to discontinue therapy. Conclusions MB oral rinse showed significant pain reduction and improved oral functioning with minimal adverse effects. Trial registration ClinicalTrials.gov ID: NCT03469284.

Methylene Blue for the Treatment of Radiation-Induced Oral Mucositis during Head and Neck Cancer Treatment: An Uncontrolled Cohort

“…In a recently published trial of MBOR for OM-related pain, patients undergoing RT were excluded from the study because of the unknown ionization effect of MBOR on radiating tissue [22]. However, when topically applied and in such low concentra-tions, an ionization effect had not been reported and was not a concern to the referring radiation oncologists.…”