Celecoxib in Reducing Cognitive Impairment with Neoadjuvant Chemotherapy or Definitive Chemoradiation for Head and Neck Carcinoma (CELCI-HN): A Phase II Randomized Trial

Abstract Purpose Chemotherapy-related cognitive impairment (CRCI) is an under-recognized consequence of cancer therapy, particularly in head and neck squamous cell carcinoma (HNSCC) patients receiving neoadjuvant chemotherapy (NACT) or definitive chemoradiation (CTRT). Celecoxib, a selective Cyclo-oxygenase-2 (COX-2) inhibitor, has demonstrated neuroprotective effects in preclinical models. Methods This single-centre, randomized, double-blind, placebo-controlled phase II trial evaluated the efficacy of celecoxib in reducing CRCI among patients with locally advanced HNSCC undergoing NACT followed by surgery or definitive CTRT. Patients were randomized (1:1) to receive celecoxib 100 mg twice daily or matched placebo for up to six months. Cognitive function (FACT-Cog), quality of life (FACT-H&N), psychological well-being (HADS), and neurocognition (PGI-BBD) were assessed at baseline, post-treatment, and at 3- and 6-month follow-up. Results Ninety-two patients were enrolled (45 placebo, 47 celecoxib). Baseline characteristics were balanced between arms. In the overall cohort, cognitive and QoL scores declined significantly from baseline to post-NACT/CTRT (FACT-Cog mean difference: 6.15; 95% CI: 1.54–10.76; p = 0.01; FACT-H&N mean difference: 9.57; 95% CI: 3.11–16.03; p = 0.004). However, no statistically significant inter-arm differences were observed at any assessment point for cognition, QoL, HADS scores, or objective neurocognitive assessment. Conclusion The addition of celecoxib (200 mg/day for six months) did not significantly impact cognitive function, quality of life, or psychological distress compared with placebo in patients with HNSCC receiving NACT or definitive CTRT. Further studies incorporating higher doses, and longer duration are warranted. Trial registration CTRI/2022/09/045579 (registered on 16/09/2022)