Randomized clinical trial of a mucoadhesive formulation containing curcuminoids (Zingiberaceae) and Bidens pilosa Linn (Asteraceae) extract (FITOPROT) for prevention and treatment of oral mucositis - phase I study.

Preclinical repeated-dose toxicity and efficiency studies developed by our group suggest the potential of FITOPROT in treating mucositis. This serious limiting side effect is observed at a rate of 40-100% in patients under antineoplastic therapy and despite different palliative measures and therapeutic agents have been investigated, still no therapy was completely successful. Therefore, this study aimed to establish the safety and recommended phase II dose of FITOPROT for the prevention and treatment of chemoradiotherapy-induced oral mucositis (OM) in patients with head and neck cancer. Twenty healthy adult participants were randomized into two groups that received pre-established concentrations of the collutory: group 1 (FITOPROT A - mucoadhesive formulation containing 10 mg/mL of curcuminoids extract plus 20% v/v of Bidens pilosa L. extract) and group 2 (FITOPROT B - mucoadhesive formulation containing 20 mg/mL of curcuminoids extract, plus 40% v/v of Bidens pilosa L. extract). Participants rinsed their mouths with FITOPROT, three times daily, for ten consecutive days. No participant experienced toxicity or unacceptable discomfort and/or adverse reactions (CTCAE v5.0), with laboratory and clinical parameters under normal conditions. Side effects observed were low intensity and temporary mucosa/dental surface pigmentation (n = 7) and tooth sensitivity (n = 4), which disappeared after formulation use ceased. No significant cellular genotoxic effects were observed (p > 0.05), and micronuclei frequencies were not changed (p > 0.05). Biochemical assays reveled no altered levels of myeloperoxidase (p = 0.2268), malondialdehyde (p = 0.1188) nor nitric oxide (p = 0.5709) concentration, and no significant difference were found in the levels of pro-inflammatory cytokines (p > 0.05). Thus, FITOPROT demonstrated to be safe and tolerable in both tested doses and is suitable for evaluation in a phase II trial as treatment against OM.