Abdulrhman, M., El Barbary, N.S., Ahmed Amin, D., & Saeid Ebrahim, R. (2012). Honey and a mixture of honey, beeswax, and olive oil-propolis extract in treatment of chemotherapy-induced oral mucositis: A randomized controlled pilot study. Pediatric Hematology and Oncology, 29, 285–292.

To evaluate the effect of topical use of honey and a mixture of honey, olive oil-propolis extract, and beeswax (HOPE) as natural products in the treatment of chemotherapy-related oral mucositis

Patients were randomly assigned to one of three groups, with 30 patients in each group. All patients used routine oral care, which included toothbrushing with a soft brush and normal saline rinses three times daily before topical treatment. All treatments were done three times daily to affected oral mucosa until healing or for 10 days, whichever came first. Topical treatments in each group were performed by the resident or nursing staff under researcher supervision.    

• Group 1 (Honey group) applied 0.5 g honey/kg (maximum 15 g) topically to affected oral mucosa.            
• Group 2 (HOPE group) used 0.25 g/kg (maximum 5 g) of a 4:2:1 mixture of honey, olive oil-propolis extract, and beeswax.                                                                 
• Group 3 (control group) received benzocaine 7.5% gel.

• The group consisted of 90 patients, ranging in age from 2–18 years old.
• Mean patient age was 6.9 years. Mean patient age was 9 years (SD = 3.8 years).
• The sample was 63% male and 37% female.
• Patients were included in the study if they
  • Had an acute lymphoblastic leukemia (ALL) diagnosis.
  • Were undergoing the consolidation phase of treatment with methotrexate.
  • Had chemotherapy-related oral mucositis grades 2 and 3 based on the National Cancer Institute Common Toxicity Criteria (NCI-CTC).
• Patients were excluded if they
  • Were diagnosed with diabetes mellitus.
  • Had received antiviral/antifungal therapy or any other treatment for oral mucositis before enrollment.
  • Were experiencing neutropenia with absolute neutrophil count (ANC) of more than 1,500.
  • Had advanced or severe periodontitis (periodontal pockets of 6 mm or greater).

The study was conducted at a single site, inpatient setting at Hematology-Oncology of Children's Hospital of Ain Shams University in Egypt.

• Patients were undergoing the active treatment phase of care.
• This study has clinical applicability for pediatrics.

This was a randomized, non-blinded, controlled, clinical phase II trial.

• The primary outcome measure was recovery time, defined as number of days from initiation of treatment to when complete healing of all ulcers occurred.    
• The NCI-CTC was used.

• In patients with grade 2 mucositis, recovery time was reduced in the honey group as compared with either the HOPE or control groups (p < 0.05).
• In patients with grade 3 mucositis, recovery time did not differ significantly between honey and HOPE (p = 0.6).
• Compared to controls, both the honey and HOPE groups had significantly faster healing (p < 0.01).
• Comparing both grades, honey produced faster healing as compared with either control (p = 0.005; statistical power of 96.2%) or HOPE (p = 0.0056; statistical power of 81.9%).

The superiority of topical honey alone may be related to the amount of honey used as well as better distribution in the oral cavity.

• The sample size was small with fewer than 100 patients.
• The study was not blinded to both researcher and patient.
• The study only involved a select group (pediatrics).
• The authors have a pending patent application for the mixture of honey, beeswax, and olive oil-propolis extract.
• No description was provided regarding the management of mucositis in the control group.
• No information was provided about other treatments for mucositis-related pain.

Mucositis is a significant debilitating side effect of cancer therapy. Effective interventions to reduce or eliminate the severity of this symptom are needed. Further research is needed in all patient populations.