Ibuprofen gargle for chemo- or Chemoradiotherapy-induced Oral Mucositis: a feasibility study

Abstract

Background: Oral mucositis frequently occurs in cancer patients treated with chemotherapy and chemoradiotherapy (CRT). This study examined the safety and efficacy of ibuprofen gargle in healthy volunteers and patients with chemotherapy-and concomitant CRT-induced oral mucositis. Methods: We enrolled healthy volunteers and patients with chemotherapy-and CRT-induced oral mucositis. In cohort I, single and multiple doses of ibuprofen gargle (0.6% or 1.0%) were administered to healthy volunteers on day 1 and days 4-10. In cohort II, multiple doses of ibuprofen gargle (0.6%) were administered to patients with complicated grade 2-3 oral mucositis based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The primary endpoint of cohort I was the treatment-related adverse events (TRAEs) as defined by CTCAE version 4.0. The primary endpoint of cohort II was the change in the visual analogue scale (VAS) pain score from before to 15 min after gargle use on day 3. The incidence and severity of TRAEs were assessed based on the CTCAE version 4.0 and a subjective rating scale completed by healthy volunteers and patients. Results: In cohort I, 9 of 10 healthy volunteers were evaluable for safety. All 9 healthy volunteers reported the TRAE of oral irritation with single or multiple use of the gargle. In cohort II, 10 patients were enrolled and evaluable for safety and 7 of 10 patients were evaluable for efficacy. The mean change in the VAS pain score from before to 15 min after using the gargle on day 3 was − 1.28 (95% confidence interval: − 2.06, − 0.51), and all patients experienced some degree of pain relief (range: − 0.2 to − 2.5). All 10 patients reported the TRAE of oral irritation. No other TRAEs of ibuprofen gargle were observed in the healthy volunteers and patients. Conclusion: Despite oral irritation, the ibuprofen gargle appeared to be safe and effective for the pain related to chemo-or CRT-induced oral mucositis. However, ibuprofen-related oral irritation warrants further formulation improvement. Trial registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000014433).

Efficacy of Ibuprofen Gargle for Postoperative Pain After Mandibular Third Molar Extraction: A Phase II, Placebo-Controlled, Double-Blind, Randomized Crossover Trial

“…In a previous report on healthy subjects and patients with chemotherapy/chemoradiotherapy-associated oral mucositis [19], the mean ΔVAS and ΔVAS standard deviation (SD) of pain relief after 3 days of use were -1.28 and 0.84 (n = 7 patients), respectively, of which the pre-use VAS value of ibuprofen gargle was more than 3. In the subgroup with a VAS of 3 or more before ibuprofen gargle use, the ΔVAS was -1.56 and the ΔSD was 0.81 (n = 5).…”

“…We have reported that there were no major safety concerns and that some pain relief was obtained with an ibuprofen gargle in patients with chemo-or chemoradiotherapy-induced oral mucositis [19]. Ibuprofen gargles are retained in the mouth for about 1 minute and then spat out, so it is unlikely that ibuprofen will be absorbed into the body.…”

“…We hypothesized that an oral gargle containing dissolved ibuprofen (0.6% or 1.0%) that could be delivered directly to the affected area could contribute to pain relief for oral mucositis. It has been reported that there were no major safety concerns and that some pain relief was obtained for chemotherapy/chemoradiotherapy-associated oral mucositis [19].…”

Efficacy of Ibuprofen Gargle for Postoperative Pain After Mandibular Third Molar Extraction: Protocol for a Phase II, Placebo-Controlled, Double-Blind, Randomized Crossover Trial

“…We hypothesized that an oral gargle containing dissolved ibuprofen (0.6% or 1%) delivered directly to the affected area could contribute to pain relief for oral mucositis. In our previous study, we have reported that there are no major safety concerns and that some pain relief is obtained for chemotherapy- or chemoradiotherapy-associated oral mucositis [ 25 ].…”

“…It is hoped that ibuprofen-containing gargles will provide an efficient drug delivery system targeting the painful area after tooth extraction, with minimal systemic effects. An unresolved limitation of our previous study [ 25 ] is that it was not possible to estimate the extent to which a placebo effect may have been present because the study was an uncontrolled trial involving healthy adults and patients with chemotherapy- or chemoradiotherapy-associated oral mucositis [ 25 ].…”