The Efficacy of Celecoxib During Chemoradiation in Locally Advanced Head and Neck Carcinoma; A Phase 2 Randomized Placebo-Controlled Clinical Trial

Abstract

Background: Cyclo-oxygenase-2 (COX-2), an enzyme induced in pathological states, mediates the production of prostaglandins. Celecoxib as a selective COX-2 inhibitor may affect the outcome of treatments in several cancer types. Objectives: We conducted a randomized controlled double-blind clinical trial to evaluate the toxicity and efficacy of celecoxib administered concurrently with chemoradiation in locally advanced head and neck carcinomas. Methods: Patients with locally advanced head and neck carcinoma referred for definitive chemoradiation were eligible to enter the study. Celecoxib (100mg, qid, oral) or placebo was administered all over the chemoradiation period. Results: Totally, 122 patients were enrolled. Patients in the celecoxib group had a longer median time to onset of grade 2 mucositis (56 days vs. 28 days, P < 0.001) and a lower rate of grade 3 mucositis (1.6% vs. 21.3%, P = 0.001). The 4-year progression-free survival was significantly higher in the celecoxib group (P = 0.0013). Conclusions: This study revealed that utilizing celecoxib may lead to better tumor local control and delayed and reduced mucosal side effects of chemoradiation.

The Efficacy and Safety of Celecoxib in Addition to Standard Cancer Therapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…Then we reviewed the full texts of the selected 102 studies and excluded 72 studies due to irrelevant data. Finally, 30 studies were included in this meta-analysis ( Figure 1 ) [ 29 , 30 , 31 , 32 , 33 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ].…”

“…As to second chemoprevention, celecoxib is an effective agent for the prevention of colorectal adenomas and familial adenomatous polyposis [ 14 , 77 ]. In terms of tertiary chemoprevention, also known as the clinical therapy phase, clinical studies reported that celecoxib improved the clinical efficacy of breast cancer, gastric cancer, rectal cancer, colorectal cancer, and head and neck cancer [ 29 , 30 , 46 , 50 , 56 ]. Celecoxib may exert its anticancer effects by reducing the production of COX-2-dependent PGE 2 and then inhibiting the COX-2/PGE 2 /EP 2 /p-AKT/p-ERK and PGE 2 /NF-kB pathways [ 25 , 26 ].…”

“… Efficacy of celecoxib-combined palliative therapy in different cancer types on overall survival (OS) ( A ) and progression-free survival (PFS) ( B ). HR: hazard ratio; CI: confidence interval [ 29 , 31 , 41 , 42 , 48 , 50 , 51 , 52 , 56 , 58 , 59 , 60 , 61 , 62 , 63 ]. …”