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

Terence T. Sio, Miran J. Blanchard, Paul J. Novotny, Samir H. Patel, Jean Claude M. Rwigema, Levi D. Pederson, Lisa A. McGee, Mauricio E. Gamez, Grant R. Seeger, James A. Martenson, Yvonne Grover, Michelle A. Neben Wittich, Yolanda Isabel Garces, Robert L. Foote, Robert C. Miller, Michele Y. Halyard

Research output: Contribution to journalArticle

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

Original languageEnglish (US)
Pages (from-to)1814-1824
Number of pages11
JournalMayo Clinic proceedings
Volume94
Issue number9
DOIs
StatePublished - Sep 1 2019

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Mucositis
Acetylcysteine
Chemoradiotherapy
Neck
Randomized Controlled Trials
Head
Xerostomia
Saliva
Radiotherapy
Placebos
Viscosity
Area Under Curve
Mouth
Eating
Quality of Life
Organizations
Pain
Research

ASJC Scopus subject areas

  • Medicine(all)

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N-Acetylcysteine Rinse for Thick Secretion and Mucositis of Head and Neck Chemoradiotherapy (Alliance MC13C2) : A Double-Blind Randomized Clinical Trial. / Sio, Terence T.; Blanchard, Miran J.; Novotny, Paul J.; Patel, Samir H.; Rwigema, Jean Claude M.; Pederson, Levi D.; McGee, Lisa A.; Gamez, Mauricio E.; Seeger, Grant R.; Martenson, James A.; Grover, Yvonne; Neben Wittich, Michelle A.; Garces, Yolanda Isabel; Foote, Robert L.; Miller, Robert C.; Halyard, Michele Y.

In: Mayo Clinic proceedings, Vol. 94, No. 9, 01.09.2019, p. 1814-1824.

Research output: Contribution to journalArticle

Sio, TT, Blanchard, MJ, Novotny, PJ, Patel, SH, Rwigema, JCM, Pederson, LD, McGee, LA, Gamez, ME, Seeger, GR, Martenson, JA, Grover, Y, Neben Wittich, MA, Garces, YI, Foote, RL, Miller, RC & Halyard, MY 2019, 'N-Acetylcysteine Rinse for Thick Secretion and Mucositis of Head and Neck Chemoradiotherapy (Alliance MC13C2): A Double-Blind Randomized Clinical Trial', Mayo Clinic proceedings, vol. 94, no. 9, pp. 1814-1824. https://doi.org/10.1016/j.mayocp.2019.03.031
Sio, Terence T. ; Blanchard, Miran J. ; Novotny, Paul J. ; Patel, Samir H. ; Rwigema, Jean Claude M. ; Pederson, Levi D. ; McGee, Lisa A. ; Gamez, Mauricio E. ; Seeger, Grant R. ; Martenson, James A. ; Grover, Yvonne ; Neben Wittich, Michelle A. ; Garces, Yolanda Isabel ; Foote, Robert L. ; Miller, Robert C. ; Halyard, Michele Y. / N-Acetylcysteine Rinse for Thick Secretion and Mucositis of Head and Neck Chemoradiotherapy (Alliance MC13C2) : A Double-Blind Randomized Clinical Trial. In: Mayo Clinic proceedings. 2019 ; Vol. 94, No. 9. pp. 1814-1824.
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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",
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T2 - A Double-Blind Randomized Clinical Trial

AU - Sio, Terence T.

AU - Blanchard, Miran J.

AU - Novotny, Paul J.

AU - Patel, Samir H.

AU - Rwigema, Jean Claude M.

AU - Pederson, Levi D.

AU - McGee, Lisa A.

AU - Gamez, Mauricio E.

AU - Seeger, Grant R.

AU - Martenson, James A.

AU - Grover, Yvonne

AU - Neben Wittich, Michelle A.

AU - Garces, Yolanda Isabel

AU - Foote, Robert L.

AU - Miller, Robert C.

AU - Halyard, Michele Y.

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N2 - 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

AB - 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

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