A comparison of silymarin vs benzydamine rinse in the prevention of radiation-induced oropharyngeal mucositis in head and neck cancers: A randomized controlled trial

INTERVENTION: Intervention 1: Silymarin group: Patients Swish mouth with 15 ml of 0.2% silymarin solution (Silybum marianum extract, Zardband pharmaceuticals, Tehran, Iran) every 8 hours for two minutes and spit the remainder. Intervention 2: Benzydamine group: Patients Swish mouth with 15 ml of 0.15% Benzydamine solution (Benzylagine – Exir Pharmaceutical Company, Tehran, Iran) every 8 hours for two minutes and spit the remainder. CONDITION: C76.0 Malignant neoplasm of head, face and neck. ; Malignant neoplasm of head, face and neck PRIMARY OUTCOME: Grade 3 mucositis. Timepoint: Before intervention and every week after intervention for at least 5 weeks. Method of measurement: According to CTCAE v.5. SECONDARY OUTCOME: Grade 1 and 2 mucositis. Timepoint: before intervention and every week during intervention for at least 5 weeks. Method of measurement: According to CTCAE v.5. Grade 3 and 4 mucositis. Timepoint: before intervention and every week during intervention for at least 5 weeks. Method of measurement: According to CTCAE v.5. Hospitalization. Timepoint: Every week during intervention for at least 5 weeks. Method of measurement: Subjective ‐ Inquired. Mortality. Timepoint: Every week during intervention for at least 5 weeks. Method of measurement: Subjective ‐ Inquired. Mucositis onset. Timepoint: Every week during intervention for at least 5 weeks. Method of measurement: The day of the first evidence of grade 1 mucositis detected by history or examination from the day of treatment initiation ‐ according to CTCAE v.5. Mucositis recovery time. Timepoint: Every week during intervention for at least 5 weeks, and the two post‐intervention weeks. Method of measurement: The day mucositis score reaches zero from treatment termination ‐ according to CTCAE v5.0. Opioid Use. Timepoint: Every week during intervention for at least 5 weeks. Method of measurement: Any opioid use detected by subjectively. Overall survival. Timepoint: The duration of survival after 24 months (730 days) from the moment of randomization. Method of measurement: Subjective ‐ Inquired. Tube or Intravenous nutrition. Timepoint: Before intervention and every week during intervention for at least 5 weeks. Method of measurement: History and examination. INCLUSION CRITERIA: Age over 18 years old Any ECOG performance status Head and neck cancer patient Any setting of radiation (i.e. definitive, neoadjuvant, adjuvant) Receiving at least 50 Gy radiation to 2 out of 4 subsite of the head and neck, including oral cavity, Oropharynx, hypopharynx, and the larynx More than 2 cm of irradiated mucosal surface in any head and neck subsite