Oral Mucositis in Head and Neck Cancer
Conditions
Keywords
propolis, radiotherapy, oral mucositis, head and neck cancer, chemoradiotherapy, oral care, placebo controlled trial, supportive care
Brief summary
This clinical trial evaluated whether a 15% propolis solution could delay or prevent severe oral mucositis in patients with head and neck cancer receiving radiotherapy or concurrent chemoradiotherapy. Oral mucositis is a common and painful side effect of radiotherapy to the head and neck region. It can interfere with eating, swallowing, hydration, pain control, and treatment tolerance. Researchers compared propolis plus standard oral care with placebo plus standard oral care. The main question was whether propolis delayed the first occurrence of severe oral mucositis during radiotherapy. Severe oral mucositis was assessed using the World Health Organization Oral Toxicity Scale. Participants were randomly assigned to receive either 15% propolis solution or placebo. Both solutions were used with the same schedule. Participants diluted 20 drops in 50 mL water and used the assigned solution with a swish-and-swallow method four times daily during radiotherapy. All participants also received standard oral care. Participants had weekly clinical assessments during radiotherapy. Researchers recorded oral mucositis grade, swallowing difficulty, pain, need for oral nutritional supplements, clinical oral candidiasis, hospitalization for supportive care, and other treatment-related outcomes. Quality-of-life questionnaires were completed at planned study visits.
Detailed description
Radiotherapy-induced oral mucositis is a frequent and clinically important toxicity in patients receiving radiotherapy or concurrent chemoradiotherapy for head and neck cancer. Severe oral mucositis can cause pain, swallowing difficulty, reduced oral intake, dehydration, need for nutritional support, hospitalization for supportive care, and interruptions in cancer treatment. Propolis is a resinous bee-derived product containing phenolic compounds and flavonoids. It has been studied for potential anti-inflammatory, antioxidant, antimicrobial, and wound-healing effects. Because these biological properties may be relevant to the pathogenesis of oral mucositis, propolis has been proposed as a candidate supportive care intervention for patients receiving cancer therapy. This randomized, double-blind, placebo-controlled clinical trial evaluated a commercially available water-soluble 15% propolis solution in patients with head and neck cancer receiving radiotherapy or concurrent chemoradiotherapy. Participants were randomized to receive either propolis or placebo in addition to standard oral care. The assigned solution was diluted in water and used with a swish-and-swallow method four times daily during radiotherapy. The primary objective was to determine whether 15% propolis solution delayed the first occurrence of severe oral mucositis during radiotherapy. Oral mucositis was graded during scheduled weekly clinical assessments using the World Health Organization Oral Toxicity Scale. The trial also evaluated clinically relevant supportive care outcomes, including swallowing difficulty, pain, oral nutritional supplement use, clinical oral candidiasis, hospitalization for supportive care, and patient-reported quality of life. The study was conducted as an investigator-initiated supportive care trial. The manufacturer supplied the propolis and placebo solutions free of charge but had no role in study design, participant recruitment, clinical assessments, data collection, data analysis, interpretation of findings, manuscript preparation, or the decision to submit the results for publication.
Interventions
DIETARY_SUPPLEMENT15% Propolis solution
A commercially available water-soluble 15% propolis solution. Participants diluted 20 drops in 50 mL water and used the solution with a swish-and-swallow method four times daily during radiotherapy.
OTHERPlacebo Solution
A placebo solution supplied in identical amber dropper bottles and administered according to the same dilution and swish-and-swallow schedule as the propolis solution.
OTHERStandard oral care
Standard oral care included tooth brushing with a soft toothbrush and fluoride toothpaste or denture cleaning, and bicarbonate-based mouthwash after meals.
Sponsors
Ankara Oncology Research and Training Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants, care providers, investigators, and outcomes assessors were masked to treatment allocation. Propolis and placebo solutions were supplied in identical amber dropper bottles and administered using the same schedule. The randomization sequence was managed by an independent administrative secretariat. Participants were instructed not to discuss sensory characteristics of the solutions with the assessment team.
Intervention model description
Participants were randomized to one of two parallel groups: 15% propolis solution plus standard oral care or placebo plus standard oral care. Both groups used the assigned solution with the same swish-and-swallow schedule during radiotherapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of head and neck cancer * Planned to receive radiotherapy or concurrent chemoradiotherapy to the head and neck region * Able to use the assigned oral solution with the swish-and-swallow method * Able to attend weekly clinical assessments during radiotherapy * Provided written informed consent
Exclusion criteria
* Insulin-dependent diabetes mellitus * Known allergy or hypersensitivity to propolis, bee products, bee stings, or any ingredient of the study solution * Medical condition preventing safe use of the swish-and-swallow protocol * Use of another non-protocol supplement or investigational product for prevention or treatment of oral mucositis * Unable or unwilling to provide written informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Severe Oral Mucositis | From start of radiotherapy to completion of radiotherapy, assessed weekly up to approximately 7 weeks | Time from the start of radiotherapy to the first occurrence of severe oral mucositis, defined as grade 3 or higher according to the World Health Organization Oral Toxicity Scale. The scale ranges from grade 0 to grade 4, with higher grades indicating more severe oral mucositis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Moderate or Severe Oral Mucositis | From start of radiotherapy to completion of radiotherapy, assessed weekly up to approximately 7 weeks | Time from the start of radiotherapy to the first occurrence of moderate or severe oral mucositis, defined as grade 2 or higher according to the World Health Organization Oral Toxicity Scale. The scale ranges from grade 0 to grade 4, with higher grades indicating more severe oral mucositis. |
| Incidence of Dysphagia | From start of radiotherapy to completion of radiotherapy, assessed weekly up to approximately 7 weeks | Proportion of participants with dysphagia of grade 2 or higher during radiotherapy, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. The CTCAE grading system ranges from grade 1 to grade 5, with higher grades indicating more severe adverse events. |
| Incidence of Pain | From start of radiotherapy to completion of radiotherapy, assessed weekly up to approximately 7 weeks | Proportion of participants with pain of grade 2 or higher during radiotherapy, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. The CTCAE grading system ranges from grade 1 to grade 5, with higher grades indicating more severe adverse events. |
| Requirement for Oral Nutritional Supplements | From start of radiotherapy to completion of radiotherapy, assessed weekly up to approximately 7 weeks | Proportion of participants who initiated oral nutritional supplements during radiotherapy. |
| Time to Initiation of Oral Nutritional Supplements | From start of radiotherapy to completion of radiotherapy, assessed weekly up to approximately 7 weeks | Time from the start of radiotherapy to first documented use of oral nutritional supplements. |
| Hospitalization for Supportive Care | From start of radiotherapy to two weeks later than completion of radiotherapy, up to approximately 9 weeks | Proportion of participants hospitalized from the start of radiotherapy to two weeks after completion of radiotherapy for treatment-related toxicity requiring supportive care, including nutritional support, hydration, analgesic treatment, or general supportive management. |
| Clinical Oral Candidiasis | From start of radiotherapy to completion of radiotherapy, assessed weekly up to approximately 7 weeks | Proportion of participants diagnosed with clinical oral candidiasis during scheduled clinical assessments. |
| Change in Body Weight | Baseline to week 4 of radiotherapy | Percentage change in body weight from baseline to week 4 of radiotherapy. |
| Change in Serum Albumin | Baseline to week 4 of radiotherapy | Change in serum albumin level from baseline to week 4 of radiotherapy, measured in g/L, when clinically available. |
| Change in The EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) Global Health Status Score | Baseline, week 7, and week 12 | Change from baseline in the global health status score measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Scores are linearly transformed to a 0 to 100 scale. Higher scores indicate better global health status and quality of life. |
| Change in EORTC QLQ-C30 Functional Scale Scores | Baseline, week 7, and week 12 | Change from baseline in functional scale scores measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), including physical, role, emotional, cognitive, and social functioning. Scores are linearly transformed to a 0 to 100 scale. Higher scores indicate better functioning. |
| Change in EORTC QLQ-C30 Symptom Scale and Item Scores | Baseline, week 7, and week 12 | Change from baseline in symptom scale and single-item scores measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Scores are linearly transformed to a 0 to 100 scale. Higher scores indicate greater symptom burden. |
| Change in EORTC QLQ-H&N35 Symptom Scale Scores | Baseline, week 7, and week 12 | Change from baseline in head and neck cancer-specific symptom scale scores measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Cancer Module 35 (EORTC QLQ-H\&N35). Scores are linearly transformed to a 0 to 100 scale. Higher scores indicate greater symptom burden. |
| Change in EORTC QLQ-H&N35 Single-Item Symptom Scores | Baseline, week 7, and week 12 | Change from baseline in head and neck cancer-specific single-item symptom scores measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Cancer Module 35 (EORTC QLQ-H\&N35). Scores are linearly transformed to a 0 to 100 scale. Higher scores indicate greater symptom burden or more problems. |
Countries
Turkey (Türkiye)
Contacts
PRINCIPAL_INVESTIGATORSamet Özlügedik, Prof. MD, PhD
Ankara Oncology Research and Training Hospital
Outcome results
None listed