Randomized controlled clinical pilot trial of propolis for prevention of oral mucositis in adult patients receiving chemotherapy for breast cancer: preliminary results

 Oral mucositis is a major side effect of cytotoxic treatments associated with significant symptoms and increased costs. The incidence of oral mucositis in patients receiving standard chemotherapy regimens for breast cancer ranges 31-70%. Evidence-based guidelines cannot recommend effective prophylaxis for this population. Propolis is a natural substance with many biological properties, and relatively non-toxic. A dry extract of Propolis reduced severity of oral mucosa diseases and ulcers for recurrent aphthous stomatitis.

This study aimed to evaluate safety, tolerability and efficacy of a dry extract of propolis with a minimum 8% of galangin for the prevention of chemo-induced oral mucositis in patients diagnosed of breast cancer. Adult patients scheduled to receive doxorubicin and cyclophosphamide in a Teaching Hospital were recruited. Patients recently diagnosed of stage I, II or IIIA breast cancer were included. Exclusion criteria were: allergy to propolis or pollen, poor oral health, recent therapy with antibiotics, steroids or immune-suppressor drugs. Randomization was managed by an external centre. Patients were randomized to receive a dry extract of propolis with a minimum 8% of galangin 8-10 mg/kg/day plus mouth rinsing with sodium bicarbonate (intervention group) or mouth rinsing with sodium bicarbonate (control group). Prophylaxis with sodium bicarbonate was routinely used where the study took place and was not withheld. The intervention lasted 15 days starting on the first day of chemotherapy. Incidence and severity of oral mucositis were evaluated using the NCI-CTCAE v4.0 at baseline, after 5, 10, 15 and 21 days of treatment.

60 patients were randomized to experimental (n = 30) and to control group (n = 30). All were female, mean age: 51 years (range: 26-75; SD: 11.4). The incidence of oral mucositis higher than G1, in the control group was 16.67%. No patient in the experimental group developed oral mucositis graded more than G1, while 5 patients in the control group developed mucositis grade G2 or G3 (p = 0,02; chi-square test = 5,455; df:1). Two patients (6.7%) manifested suspected skin reaction to propolis. Most patients wished to continue propolis also during the next chemotherapy cycles.

This study showed that propolis was effective in the prevention of oral mucositis. Propolis resulted well tolerated and safe. Multicentre studies should test the efficacy of propolis on bigger samples.