Laboratory of Pharmacology and Cellular Toxicology, Pharmacy Faculty, Federal University of Goiás, Goiânia, GO, Brazil.
Laboratory of Oral Pathology, Dentistry Faculty, Federal University of Goiás, Goiânia, GO, Brazil.
Chem Biol Interact. 2018 Aug 1;291:228-236. doi: 10.1016/j.cbi.2018.06.010. Epub 2018 Jun 12.
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.
本研究旨在评估 FITOPROT 预防和治疗头颈部癌症患者放化疗诱导的口腔黏膜炎（OM）的安全性和推荐的 II 期剂量。20 名健康成年参与者被随机分为两组，接受预先设定浓度的漱口液：组 1（FITOPROT A-含有 10mg/mL 姜黄素提取物和 20%v/v 三叶鬼针草提取物的黏附制剂）和组 2（FITOPROT B-含有 20mg/mL 姜黄素提取物和 40%v/v 三叶鬼针草提取物的黏附制剂）。参与者每天用 FITOPROT 漱口三次，连续十天。没有参与者出现毒性或不可接受的不适和/或不良反应（CTCAE v5.0），实验室和临床参数均处于正常状态。观察到的副作用为低强度和暂时性的黏膜/牙齿表面着色（n=7）和牙齿敏感（n=4），停止使用制剂后这些副作用消失。未观察到明显的细胞遗传毒性作用（p＞0.05），微核频率也没有改变（p＞0.05）。生化检测显示髓过氧化物酶（p=0.2268）、丙二醛（p=0.1188）和一氧化氮（p=0.5709）浓度均无改变，促炎细胞因子水平也无显著差异（p＞0.05）。因此，FITOPROT 在两种测试剂量下均表现出安全性和耐受性，适合作为 OM 的治疗方法进行 II 期试验评估。
