Acetylcysteine Rinse in Reducing Saliva Thickness and Mucositis in Patients With Head and Neck Cancer Undergoing Radiation Therapy

Mayo Clinic

Status and phase: Completed; Phase 2

Conditions: Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Oral Complications; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Adenoid Cystic Carcinoma of the Oral Cavity; Mucositis; Stage III Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Verrucous Carcinoma of the Larynx; Stage II Lymphoepithelioma of the Oropharynx; Stage IVC Lymphoepithelioma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Salivary Gland Cancer; Stage II Verrucous Carcinoma of the Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Stage IVB Lymphoepithelioma of the Oropharynx; Stage IVB Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity; Stage II Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage I Lymphoepithelioma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Basal Cell Carcinoma of the Lip; Stage III Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Mucoepidermoid Carcinoma of the Oral Cavity; Stage III Mucoepidermoid Carcinoma of the Oral Cavity; Stage II Mucoepidermoid Carcinoma of the Oral Cavity; Stage I Verrucous Carcinoma of the Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage I Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVA Salivary Gland Cancer; Stage IVC Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage II Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVA Lymphoepithelioma of the Oropharynx; Stage III Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Nasopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Recurrent Salivary Gland Cancer; Stage IVB Salivary Gland Cancer; Stage III Basal Cell Carcinoma of the Lip; Stage I Salivary Gland Cancer; Stage II Basal Cell Carcinoma of the Lip; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Stage I Verrucous Carcinoma of the Larynx; Recurrent Basal Cell Carcinoma of the Lip; Stage IVB Mucoepidermoid Carcinoma of the Oral Cavity; Stage IVC Mucoepidermoid Carcinoma of the Oral Cavity; Stage I Squamous Cell Carcinoma of the Nasopharynx; Stage IVC Basal Cell Carcinoma of the Lip; Stage IVB Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage IV Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage IVC Salivary Gland Cancer; Stage II Lymphoepithelioma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Stage III Lymphoepithelioma of the Oropharynx; Stage II Verrucous Carcinoma of the Larynx; Stage I Squamous Cell Carcinoma of the Larynx; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage I Basal Cell Carcinoma of the Lip; Stage III Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage I Lymphoepithelioma of the Nasopharynx; Stage IVB Basal Cell Carcinoma of the Lip; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVA Mucoepidermoid Carcinoma of the Oral Cavity; Stage III Salivary Gland Cancer

Treatments: Other: questionnaire administration; Other: quality-of-life assessment; Other: placebo; Drug: acetylcysteine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02123511

P30CA015083 (U.S. NIH Grant/Contract)

NCI-2014-00865 (Registry Identifier)

Mod13-007632-07

MC13C2 (Other Identifier)

Details and patient eligibility

About

This randomized pilot clinical trial studies whether acetylcysteine oral rinse will lessen saliva thickness and painful mouth sores in patients with head and neck cancer undergoing radiation therapy. Side effects from radiation therapy to the head and neck, such as thickened saliva and mouth sores, may interfere with activities of daily living such as eating and drinking, and may also cause treatment to be stopped or delayed. Acetylcysteine rinse may reduce saliva thickness and mouth sores, and improve quality of life in patients with head and neck cancer undergoing radiation therapy.

Full description

PRIMARY OBJECTIVES:

I. To determine the effectiveness of N-acetylcysteine (acetylcysteine) in improving saliva viscosity (as measured by the Groningen Radiotherapy-Induced Xerostomia [GRIX]) in patients undergoing chemotherapy and radiotherapy for head and neck cancer.

SECONDARY OBJECTIVES:

I. To determine whether N-acetylcysteine (NAC) can improve other GRIX subscale for patients undergoing chemotherapy and radiotherapy for head and neck cancer.

II. To determine whether NAC can improve patient reported quality of life as measured by the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire (QLQ) Head & Neck (H&N)35.

III. To assess the adverse event profile of NAC as measured by the Common Terminology Criteria for Adverse Events (CTCAE) every week during radiation.

IV. To determine patient adherence to N-acetylcysteine mucoadherent rinse using patient reported surveys.

V. To determine the long-term benefits of N-acetylcysteine as measured by the GRIX questionnaire at 45 days and 90 days post treatment.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive acetylcysteine oral rinse and gargle or swish for 60 seconds then spit 5 times per day, beginning within 3 days of the initiation of radiotherapy to 14 days following completion of radiotherapy.

ARM II: Patients receive a placebo oral rinse and gargle or swish for 60 seconds and then spit 5 times per day beginning within 3 days of the initiation of radiotherapy to 14 days following completion of radiotherapy.

After completion of study treatment, patients are followed up at 45 and 90 days.

Enrollment: 34 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histological confirmation of tumor of the oral cavity, oropharynx, supraglottic larynx, or nasopharynx
• Receiving concurrent chemoradiotherapy/chemobiotherapy to a minimum dose equivalent to 60 Gy in 30 fractions in the adjuvant or definitive setting
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Initiation of investigational agent =< 3 days after initiation of radiotherapy
• Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
• Ability to complete questionnaire(s) by themselves or with assistance
• Provide informed written consent
• Willing to return mail-in questionnaires during the observation phase of the study

Exclusion criteria

• Any of the following:

  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception

• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

• Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; NOTE: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm

• History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

• Receipt of induction chemotherapy

• Previous receipt of head and neck irradiation

• Utilization of amifostine during radiotherapy

• Greater than or equal to grade 2 dry mouth prior to chemoradiotherapy or greater than or equal to grade 2 mucositis

• Previous intolerance/adverse effect/allergy to any component of the placebo or active agent

• History of Sjogren's, lupus or scleroderma

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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34 participants in 2 patient groups, including a placebo group

Arm I (acetylcysteine)

Experimental group

Description:

Patients receive acetylcysteine oral rinse and gargle or swish for 60 seconds then spit 5 times per day beginning within 3 days of the initiation of radiotherapy to 14 days following completion of radiotherapy.

Treatment:

Drug: acetylcysteine

Other: quality-of-life assessment

Other: questionnaire administration

Arm II (placebo)

Placebo Comparator group

Description:

Patients receive a placebo oral rinse and gargle or swish for 60 seconds and then spit 5 times per day beginning within 3 days of the initiation of radiotherapy to 14 days following completion of radiotherapy.

Treatment:

Other: quality-of-life assessment

Other: placebo

Other: questionnaire administration