N-Acetylcysteine Rinse for Thick Secretion and Mucositis of Head and Neck Chemoradiotherapy (Alliance MC13C2): A Double-Blind Randomized Clinical Trial

Abstract

Objective: To determine whether N-acetylcysteine rinse was safe and could improve thickened secretions and dry mouth during and after radiotherapy.

Patients and methods: We designed a prospective pilot double-blind, placebo-controlled randomized clinical trial (Alliance MC13C2). Adult patients (age ≥18 years) were enrolled if they underwent chemoradiotherapy (≥60 Gy). Patients initiated testing rinse within 3 days of starting radiotherapy. With swish-and-spit, they received 10% N-acetylcysteine (2500 mg daily) or placebo rinse solution 5 times daily during radiotherapy and 2 weeks postradiotherapy. The primary aim was to evaluate N-acetylcysteine in improvement of saliva viscosity with the Groningen Radiotherapy-Induced Xerostomia questionnaire. Secondary aims included evaluating xerostomia improvement by the same questionnaire and with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck-35 Questions survey and adverse-event profiles. The type I error rate was 20%.

Results: Thirty-two patients undergoing chemoradiotherapy were enrolled. Baseline characteristics were balanced for placebo (n=17) and N-acetylcysteine (n=15). N-acetylcysteine was better for improving sticky saliva (area under curve, P=.12). Scores of multiple secondary end points favored N-acetylcysteine, including sticky saliva daytime (P=.04), daytime and total xerostomia (both P=.02), pain (P=.18), and trouble with social eating (P=.15). Repeated measures models confirmed the findings. Taste was a major dissatisifer for N-acetylcysteine rinse; however, both testing rinses were safe and well tolerated overall.

Conclusion: Our pilot data showed that N-acetylcysteine rinse was safe and provided strong evidence of potential efficacy for improving thickened saliva and xerostomia by patient-reported outcome. A confirmatory phase 3 trial is required.

Trial registration: clinicaltrials.gov Identifier: NCT02123511.

Copyright © 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.

Consolidated Standards of Reporting Trials (CONSORT) Flow Diagram for the MC13C2 (Alliance for Clinical Trials in Oncology) Trial. This randomized trial evaluated placebo rinse (arm A) vs NAC rinse (arm B) for thickened secretions and mucositis during head and neck chemoradiotherapy. The primary end point is the area under the curve for Groningen Radiation-Induced Xerostomia sticky saliva total score. Asterisk indicates evaluable for primary end point. AE = adverse events; NAC = N-acetylcysteine.

Figure 2.

GRIX Xerostomia and Sticky Saliva Scores by Trial Arms. A, GRIX xerostomia daytime score (AUC score for first 3 cycles; P=.02). B, GRIX xerostomia total score (P=. 02). C, GRIX sticky saliva daytime score (P=.04). D, GRIX sticky saliva total score (P=.12). For cycle numbers, 0 indicates baseline, 1-8 indicate weekly measurements during RT, and 9-11 indicate 14, 45, and 90 days post RT, respectively. Arm A = placebo rinse; Arm B = NAC rinse; AUC = area under the curve; GRIX = Groningen Radiation-Induced Xerostomia; NAC = N-acetylcysteine; RT= radiotherapy.