9620 Background: Oral mucositis (OM) is a painful complication of radiation therapy (RT) for head and neck (H&N) cancer. OM can compromise nutrition, require opioid analgesics and hospitalization for pain control, and lead to treatment interruptions. Due to the role of inflammatory pathways in the pathogenesis of OM, this study investigated the effect of inhibition of cyclooxygenase-2 (COX-2) on severity and morbidity of OM. Methods: In this randomized double-blind placebo-controlled trial,40 H&N cancer patients were randomized to daily use of 200 mg celecoxib or matched placebo, for the duration of RT. Eligibility criteria included planned RT dose of ≥ 5000 cGy to 2+ areas of the mouth and no contraindication for celecoxib use. The planned sample size of 20 per arm provided 80% power to detect a 1 point difference in mean Oral Mucositis Assessment Scale (OMAS) score (range 0-5) at 5000 cGy RT (primary endpoint), applying a two-tailed, two-sample t-test at the 5% level of significance. Clinical OM, normalcy of diet, pain scores and analgesic use were assessed 2-3 times a week by blinded investigators during the 6-7 week period of RT, using validated scales. Results: Twenty subjects were randomized to each arm, which were similar with respect to tumor location, radiation dose, and concomitant chemotherapy. In both arms, mucositis and pain scores increased over the course of RT. Intent-to-treat analyses demonstrated no significant difference in mean (SD) OMAS scores at 5000 cGy [celecoxib 1.32 (0.71), placebo 1.27 (0.86), p = 0.83, two sample t-test]. There was also no difference between the celecoxib and placebo arms respectively, in mean OMAS scores over the period of RT (SD) [0.98(0.77) & 0.97 (0.86), p = 0.84], mean worst pain scores [3.38 (3.07) & 3.31 (3.32), p = 0.83], mean normalcy of diet scores [5.43 (3.86) & 5.11(3.94), p = 0.65], or mean daily opioid medication use in IV morphine equivalents [19.08 (16.57) & 20.48 (19.07), p = 0.48], all by linear mixed model fixed effects regression analysis. There were no SAEs attributed to celecoxib use. Conclusions: Daily use of a selective COX-2 inhibitor, during the period of RT for H&N cancer, did not reduce the severity of clinical OM, pain, dietary compromise or use of opioid analgesics. Clinical trial information: NCT00698204.
A randomized, double-blind, placebo-controlled trial of a COX-2 inhibitor (Rofecoxib) in patients undergoing coronary artery bypass surgery
