Propolis for prevention of chemo-induced oral mucositis in breast cancer patients: A randomized controlled trial

Abstract

Background: Oral mucositis is a major side effect of cytotoxic treatments associated with clinically significant symptoms and increased costs. The incidence of oral mucositis in patients receiving standard chemotherapy regimens for breast cancer ranges 31-70%. The available evidence-based guidelines cannot recommend any effective prophylaxis for this cancer population. Propolis is a natural substance with many biological properties, and relatively non-toxic. A dry extract of Propolis has reduced the severity of oral mucosa diseases and oral ulcers in patients diagnosed with recurrent aphthous stomatitis. Methods and Materials: This study aimed to evaluate safety, tolerability and preliminary clinical 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. Patients scheduled to receive doxorubicin and cyclophosphamide in a Teaching Hospital from May 2012 to February 2015 were recruited. Inclusion criteria were: >20 years old, recently diagnosed of stage I, II or IIIA breast cancer. Exclusion criteria were: allergy to propolis, pollen, allergic predisposition or atopy, poor oral health, recent therapy with antibiotics, chronic therapy with steroids or immune-suppressor drugs. Randomization was performed through a computer-generated table and managed by an external centre. Eligible patients were randomized either 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). Sodium bicarbonate rinses were routinely used where the study took place and were 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. Tolerability of propolis and adverse events were also recorded. Results: 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 during the first cycle 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 (n = 4) or G3 (n = 1) with a statistically significant difference (p = 0.02; chi-square test=5,455; df:1). Two patients (6.7%) manifested suspected skin reaction to propolis. Propolis resulted well tolerated and most patients wished to continue prophylaxis with propolis also during the next cycles. Conclusion: This one-site pilot study showed that propolis was effective in the prevention of oral mucositis. Multicentre studies should test the efficacy of propolis on bigger samples.