Prophylaxis of oral mucositis associated with chemoradiotherapy for oral carcinoma by Azelastine hydrochloride (Azelastine) with other antioxidants.

Background: One of the dose-limiting adverse effects of chemoradiotherapy is mucositis, especially oral mucositis. Prophylaxis of severe mucosal reaction would allow application of aggressive chemoradiotherapy to malignancies.

Methods: Sixty-three patients who received inductive concomitant chemoradiotherapy with cobalt 60 (60Co, approximately 30 Gy), peplomycin (PLM, approximately 38 mg), and 5-fluorouracil (5-FU, approximately 3,500 mg) were included in this study. From the start of therapy to the disappearance of oral erosion, 37 patients received daily doses of Azelastine (2 mg) + vitamin C (500 mg) + vitamin E (200) + glutathione (200 mg) (azelastine group), whereas the other 26 patients received the same regimen without azelastine (control group). The severity of oral mucositis in both groups was evaluated periodically.

Results: At 10 Gy with 15 mg PLM and 1,250 mg 5-FU, grade 1 mucositis (redness of the oral mucosa) was induced in 14 patients in the control group and five patients in the Azelastine group. At 20 Gy with 30 mg PLM and 2,500 mg 5-FU, grade 2 (erosion with mild irritation) and grade 3 (extensive erosion with marked irritation) stomatitis were observed in 9 and 3 of the control patients and 5 and 1 in the Azelastine group, respectively. At the completion of treatment, mucositis in 21 patients in the Azelastine group remained at grade 1 or grade 2, whereas grades 3 and 4 (ulceration with severe contact pain) mucositis were observed in 6 and 10 patients, respectively. However, in the control group, grades 1 and 2 were observed in only 2 and 3 cases, whereas grades 3 and 4 stomatitis were induced in 6 and 15, respectively. Azelastine suppressed neutrophil respiratory burst both in vivo and in vitro, and also suppressed cytokine release from lymphocytes. However, neutrophil superoxide dismutase (SOD) activity was negligibly suppressed.

Conclusion: A regimen including Azelastine, which suppresses reactive oxygen production and stabilizes cell membranes, may be useful for the prophylaxis of mucositis due to chemoradiotherapy.