Aghamohammadi, A., Moslemi, D., Akbari, J., Ghasemi, A., Azadbakht, M., Asgharpour, A., & Hosseinimehr, S.J. (2018). The effectiveness of Zataria extract mouthwash for the management of radiation-induced oral mucositis in patients: A randomized placebo-controlled double-blind study. Clinical Oral Investigations, 22, 2263–2272.

Primary: To evaluate the use of Zataria multiflora (ZM) extract mouthwash to reduce the incidence and severity of oral mucositis (OM) in adult patients with head and neck cancer undergoing radiation therapy alone or combined radiation and chemotherapy. 

Secondary: The impact of ZM extract mouthwash on the amount of opioid used, the use of anti-inflammatory drug use, antibiotic use, and body weight over the course of therapy

• Double blinded, randomized
• Intervention group: Used a mouthwash containing ZM extract
• Control group: Used a placebo mouthwash with no ZM extract
• Both groups: Oral examination prior to initiation of therapy and then weekly until completion of the last radiation dose. Participants encouraged to use the mouthwash three times daily (after breakfast and lunch and at bedtime) in addition to one half hour prior to each radiation session. Maintained for seven weeks after therapy (data collected only until the end of therapy). Participants instructed to not rinse mouth with water up to one hour after gargling with mouthwash. Participants were also instructed not to smoke or eat hot, spicy, or very cold foods. Oral analgesics and anti-inflammatory medications were given as needed and per standard of care.

• N: 63 patients randomized, 25 in treatment group (16% attrition) and 27 in placebo group (20% attrition)   
• AGE: 57.48 years (SD = 17.98) in treatment group, 64.62 years (SD = 12.75) in placebo group
• MALES: 71%  
• FEMALES: 29%
• CURRENT TREATMENT: Radiation, combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Head and neck cancer (radiation [at least 6000 cGy] planned for the entire oropharynx, nasopharynx, and/or greater than one-third of the oral cavity, a KPS > 70, with or without chemotherapy)
• OTHER KEY SAMPLE CHARACTERISTICS: No prior history of head and neck radiation, no current poor oral hygiene, no active infections of the mouth, no liver or kidney disease, no diabetes, no autoimmune disease or disease that might alter healing

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: Iran

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS: Elder care

Double blinded, randomized, placebo controlled study

• World Health Organization (WHO) mucositis scale
• Oral Mucositis Assessment Scale (OMAS)
• Visual analogue score (VAS) for pain
• Required opioid analgesia (weekly)
• Required anti-inflammatory drugs (weekly)
• Required antibiotics (weekly)
• Weekly body weights

Primary outcomes: 

• The presence and intensity of OM the groups was significantly different using the OMAS for all six weeks of assessment (p < 0.05 [range = 0.002-0.016]) and for weeks 3, 4, and 6 using the WHO OM scale (p < 0.05 [range = 0.009-0.045]) favoring the ZM group. There was a decrease in the incidence of grades 3-4 OM in the ZM group in comparison to the placebo group (24% versus 55.5%).

Secondary outcomes: 

• Pain: The ZM group demonstrated a lower pain score in weeks 2-6
• Weight loss: Less in the ZM group (p = 0.000)
• Required analgesia: Less in the ZM group (p = 0.010)
• Antibiotic use: Less in the ZM group (p = 0.037)

The use of ZM mouthwash positively impacted the incidence and severity of OM in patients with head and neck cancer undergoing head and neck radiation with or without concurrent chemotherapy. In addition, the ZM mouthwash contributed to less use of opioid analgesia, less antibiotic use, and decreased weight loss.

• Small sample (< 100)
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: It is hard to discern how analgesic and anti-inflammatory use was ascertained.

ZM may offer an option for decreasing OM in patients undergoing radiation with or without concurrent chemotherapy in the head and neck cancer population.