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Mucoadhesive clonidine (Clonidine Lauriad) in the prevention of severe radiomucositis in head and neck cancer patients: A phase II randomized trial.
Background: Oral mucositis (OM) is the most frequent and severe complication of chemoradiotherapy (CRT) in head and neck cancer patients. There is currently no effective mechanistically-targeted intervention for CRT-induced OM. NF-κB plays a central role in the signaling cascades and pathways responsible for OM. Clonidine reduces NF-κB activation and the subsequent expression of pro-inflammatory cytokines. In preclinical studies, topical clonidine reduced the incidence and duration of severe OM (SOM). The safety and efficacy of 2 doses of clonidine MBT were evaluated in patients with head and neck cancer receiving postoperative CRT. Methods: This phase 2, multicenter, double-blind, randomized, placebo-controlled, 3-arm study compared clonidine MBT 50µg, 100µg, and placebo. Clonidine MBT and matching placebo were applied to the gum once daily 1-3 days prior to RT until the end of CRT. The primary endpoint was the cumulative radiation dose at the onset of SOM (WHO grade 3 or 4) analyzed by the Kaplan-Meier method and the log-rank test. Safety was evaluated by monitoring AEs, clinical laboratory parameters, vital signs, and physical examinations. Results: Clonidine MBT was administered to 121 patients and placebo to 62. SOM developed in 45.3% of patients in the clonidine MBT group and in 60.0% of patients in the placebo group (p = 0.064). Patients developed SOM at a median radiation dose of 60.0 Gy and 48.0 Gy for the clonidine MBT and placebo groups, respectively (HR = 0.754 [0.484; 1.175]; p = 0.211). The percentage of AEs was similar between placebo (98.4%) and clonidine MBT groups (90.8%) with less nausea (49.6% vs 71%) and dysphagia (32.8% vs 48.4%) in the clonidine MBT groups vs placebo. Conclusions: Here, we present for the first time, that clonidine MBT treatment in head and neck cancer patients undergoing postoperative CRT reduces SOM with minimal toxicity. However not statistically significant, the observed differences in the incidence and time to occurrence of SOM support the initiation of future confirmatory studies. Clinical trial information: NCT01385748