Efficacy and safety of rebamipide liquid for chemoradiotherapy-induced oral mucositis in patients with head and neck cancer: a multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II study.

BACKGROUND: Recent preclinical and phase I studies have reported that rebamipide decreased the severity of chemoradiotherapy-induced oral mucositis in patients with oral cancer. This placebo-controlled randomized phase II study assessed the clinical benefit of rebamipide in reducing the incidence of severe chemoradiotherapy-induced oral mucositis in patients with head and neck cancer (HNC). METHODS: Patients aged 20-75 years with HNC who were scheduled to receive chemoradiotherapy were enrolled. Patients were randomized to receive rebamipide 2% liquid, rebamipide 4% liquid, or placebo. The primary endpoint was the incidence of grade ≥ 3 oral mucositis determined by clinical examination and assessed by central review according to the Common Terminology Criteria of Adverse Events version 3.0. Secondary endpoints were the time to onset of grade ≥ 3 oral mucositis and the incidence of functional impairment (grade ≥ 3) based on the evaluation by the Oral Mucositis Evaluation Committee. RESULTS: From April 2014 to August 2015, 97 patients with HNC were enrolled, of whom 94 received treatment. The incidence of grade ≥ 3 oral mucositis was 29% and 25% in the rebamipide 2% and 4% groups, respectively, compared with 39% in the placebo group. The proportion of patients who did not develop grade ≥ 3 oral mucositis by day 50 of treatment was 57.9% in the placebo group, whereas the proportion was 68.0% in the rebamipide 2% group and 71.3% in the rebamipide 4% group. The incidences of adverse events potentially related to the study drug were 16%, 26%, and 13% in the placebo, rebamipide 2%, and rebamipide 4% groups, respectively. There was no significant difference in treatment compliance among the groups. CONCLUSIONS: The present phase II study suggests that mouth washing with rebamipide may be effective and safe for patients with HNC receiving chemoradiotherapy, and 4% liquid is the optimal dose of rebamipide. TRIAL REGISTRATION: ClinicalTrials.gov under the identifier NCT02085460 (the date of trial registration: March 11, 2014).

Internal jugular vein thrombosis and pulmonary thromboembolism after head and neck reconstructive surgery.

BACKGROUND: Free flap failure secondary to internal jugular vein thrombosis (IJVT) is a significant complication after head and neck reconstructive surgery. A consensus has not yet been reached among reconstructive surgeons regarding the treatment of IJVT. METHODS: We retrospectively evaluated the incidence of IJVT in 118 patients who underwent free flap reconstruction at Hyogo Cancer Center, Akashi, Japan. The occurrence of IJVT-related flap circulation crisis and pulmonary thromboembolism (PTE) was studied. This study was approved by the institutional ethics committee, and written informed consent was obtained from each patient. RESULTS: From 118 patients who underwent head and neck reconstructive surgery, we included 116 internal jugular veins (IJVs) preserved after neck dissection in the present study. IJVT was confirmed in 25 (21.6%) IJVs from 23 patients. One patient (0.8%) developed venous congestion due to IJVT, which resulted in total flap necrosis. Two patients (1.7%) exhibited PTE associated with IJVT. They were treated with direct oral anticoagulants for 3 months and were discharged without any sequelae. CONCLUSION: Our results suggest that IJVT after head and neck reconstructive surgery caused not only flap circulation crisis but also PTE. Reconstructive surgeons should be aware of the potential risks due to serious complications associated with IJVT.