Marucci, L., Farneti, A., Di Ridolfi, P., Pinnaro, P., Pellini, R., Giannarelli, D., . . . Sanguineti, G. (2017). Double-blind randomized phase III study comparing a mixture of natural agents versus placebo in the prevention of acute mucositis during chemoradiotherapy for head and neck cancer. Head and Neck, 39, 1761–1769.

To test the effectiveness of four natural compounds (propolis, aloe vera, calendula, and chamomile) in the prevention of acute mucositis during chemoradiotherapy for head and neck cancer.

The patients were randomized to receive a mixture of the natural ingredients or placebo. All patients received dental and nutritional evaluations and were allowed to use standard supportive care such as baking soda mouth rinses, NSAIDs, opioids, and IV hydration. The placebo had the same volume, color, flavor, and density as the experimental solution. The pharmacist who dispensed the study drugs managed the randomization list. Patients were instructed to rinse with 7 ml four times per day (before each meal and RT) during weekdays and before each meal (three times per day) on weekends. Weekly interviews were conducted along with a physical examination, including visual inspection of the oral cavity and the oropharynx, by a nurse and a radiation oncologist. Body weight, objective mucositis, pain control, and dysphagia were assessed during these visits.

• N = 104   
• AGE: median = 57 years
• MALES (%): 86.45  
• FEMALES (%): 13.55
• CURRENT TREATMENT: Combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Head and neck
• OTHER KEY SAMPLE CHARACTERISTICS: Squamous cell carcinoma of the oral cavity, pharynx, or larynx. Squamous cell carcinoma in the neck of unknown primary. Previously untreated with chemotherapy or radiation therapy for head and neck cancer, good oral intake with no feeding tubes (NG or PEG) at study entry, and ECOG 0-1.

• SITE: Single site   
• SETTING TYPE: Not specified    
• LOCATION: Regina Elena National Cancer Institute, Rome, Italy

PHASE OF CARE: Active anti-tumor treatment

Phase III double-blind randomized placebo controlled; 1:1 experimental versus control

CTCAE, version 3.0, was used for grading mucositis. The Verbal Descriptor Scale was used for assessing pain. Locoregional control and OS were computed with the Kaplan-Meier method from the last day of treatment and comparison was done with the log-rank test (These were included in the secondary endpoints of the study).

No difference was noted between arms.

The prophylactic use of the natural agent combination, propolis, aloe vera, calendula, and chamomile, did not show a benefit versus placebo in the prevention of oral mucositis for patients with head and neck cancer receiving chemoradiotherapy.

This was a well-conducted single-site clinical trial.

Use of natural ingredients for supportive care in oncology is usually preferable to more expensive, hard to access pharmacologic interventions. However, if the evidence does not support their use, even natural ingredients should not be used due to potential increase costs and untoward effects. Nurses play an important role in patient and HCP education about evidence-based interventions.