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

Mayo Clin Proc. 2019 Sep;94(9):1814-1824. doi: 10.1016/j.mayocp.2019.03.031. Epub 2019 Aug 9.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Aged
  • Chemoradiotherapy / adverse effects*
  • Chemoradiotherapy / methods
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Male
  • Middle Aged
  • Mouth Mucosa / drug effects
  • Mouthwashes / pharmacology*
  • Mucositis / etiology
  • Mucositis / therapy*
  • Patient Reported Outcome Measures
  • Patient Safety
  • Pilot Projects
  • Prospective Studies
  • Quality of Life
  • Reference Values
  • Risk Assessment
  • Treatment Outcome
  • Xerostomia / drug therapy*
  • Xerostomia / etiology

Substances

  • Mouthwashes
  • Acetylcysteine

Associated data

  • ClinicalTrials.gov/NCT02123511