Benzydamine for Patients Receiving Combination Chemotherapy and Radiation Therapy

To determine the efficacy of royal jelly on oral mucositis in patients receiving chemotherapy and radiation

Patients were divided into two groups. All patients received benzydamine hydrochloride and nystatin rinses. In the experimental group, royal jelly was swished orally for 30 seconds and then swallowed twice per day for a total of 1 g per day. Patients could not eat or drink within 30 minutes of using the royal jelly. Both groups used the mouthwash protocol or mouthwash protocol plus royal jelly until mucositis was resolved. All participants and assessors were blinded to group. Oral mucosa was divided into five sites—labial mucosa, buccal mucosa, gingivae, tongue, and soft and hard palates—and the mucositis score was determined daily by a trained researcher for each site until no further evidence of mucositis existed.

• N = 103  
• AGE = 52.25 years
• MALES: 47%, FEMALES: 53%
• KEY DISEASE CHARACTERISTICS: Multiple types of cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Multiple stages of cancer, chemotherapy types, and chemotherapy cycles

• SITE: Single site    
• SETTING TYPE: Outpatient    
• LOCATION: Turkey

• PHASE OF CARE: Active antitumor treatment

• Prospective, randomized clinical trial

• World Health Organization criteria for mucositis

No statistical difference was seen in mucositis severity at the beginning of the study between the two groups. For grade 1 mucositis, the mean number of days to healing in the royal jelly group was 1.1 days, and in the control group it was 2.7 days (U = 64; p = 0.0001). For grade 2 mucositis, the mean number of days to healing in the control group was 5.8 days, and in the experimental group it was 3 days (U = 77; p = 0.0001). For grade 3 mucositis, those in the experimental group had a faster healing time than those in the control group (U = 59; p = 0.005).

The addition of royal jelly to a mouthwash protocol with benzydamine and nystatin rinses significantly decreased the healing time for grade 1, 2, and 3 oral mucositis.

• Risk of bias (no random assignment)
• Other limitations/explanation: Random assignment was not described in the study

Royal jelly should be considered as an additional intervention to promote the healing of oral mucositis caused by chemotherapy and radiation. Royal jelly, in addition to a mouthwash protocol consisting of a benzydamine and nystatin rinse, effectively reduced the number of days to complete healing of oral mucositis. The sample in this study included a wide variety of cancer types as well as a wide range of types of chemotherapy and number of chemotherapy cycles.

To summarize the evidence around the use of radiotherapy, standard-dose chemotherapy, and high-dose chemotherapy with or without total body irradiation plus hematopoietic stem cell transplantation (HSCT) for the management of mucositis

• Databases searched were the Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO).
• Evidence was evaluated based on the American Society of Clinical Oncology (ASCO) Levels of Evidence (I-V) and Grades of Recommendation (A-D). Statements without grading were considered justified standard clinical practice by the expert authors and the European Society for Medical Oncology (ESMO) faculty.

• Institutions should develop oral care protocols based on clinical practice and interdisciplinary involvement. Staff and patient education are essential. Basic oral care should include saline mouth rinses 4–6 times per day and use of a soft toothbrush replaced on a regular basis. 
• Patient-controlled analgesic (PCA) with morphine is recommended for the treatment of pain in patients with oral mucositis undergoing HSCT.
• Regular oral pain assessment and topical anesthetics can provide short-term pain relief. 
• Chlorhexidine rinses are not recommended to treat established mucositis but may be an option to enhance treatment of oral infection.
• Benzydamine oral rinse is recommended for prevention of mucositis in patients with head and neck cancer receiving radiotherapy.
• For prevention of mucositis in patients receiving standard-dose chemotherapy,
  • Oral cryotherapy for 30 minutes is recommended in patients receiving fluorouracil (5-FU).
  • Keratinocyte growth factor-1 (palifermin) 40 mcg/kg per day for three days may be useful in patients receiving bolus 5-FU plus leucovorin.
• For prevention of mucositis in patients receiving high-dose chemotherapy with or without total body irradiation plus HSCT, the following are recommended.
  • Palifermin 60 mcg/kg per day for three days prior to transplant and three days post-transplant
  • Cryotherapy in high-dose melphalan
  • Low-level laser therapy (LLLT) before HSCT

The primary author was the principal investigator on the National Institutes of Health (NIH) R13 Conference Grant that provided partial support for the symposium “Oral Complications of Emerging Cancer Therapies,” 14-15 April 2009, Bethesda, MD, USA. Production of a Journal of the National Cancer Institute (JNCI) Monograph for conference publications was supported by an unrestricted educational grant form Biovirum, which owned palifermin at the time of the publication. Peterson also is a member of the Scientific Advisory Board and a paid consultant for the GI Co., Inc, which is responsible for the development of recombinant intestinal trefoil factor, for which the phase II study is cited in the references.

The mucositis guidelines reported contain few changes from the previous two versions of the ESMO Clinical Practice Guidelines. With the 2009 MASCC/ISCO Mucositis Study Group in June 2009, it was decided that no new guidelines were warranted based on the current published literature. Progress has been made in the understanding of molecular basis of mucositis. Evidence-based, cancer-specific identification of risk factors and management of mucositis depend on clinical research so that approval of new drugs and devices will be possible.