Phase I study of copaiba aqueous mouthwash in patients with head and neck cancer undergoing radiotherapy.
Authors: dos Santos Menezes Ana Carolina , Alves Lísia Daltro Borges , da Costa Ana Maria Dias , Dias Fernando Luiz , Carvalho Juliana Chaves Carneiro , Antunes Heliton Spindola , Melo Andreia Cristina De 
Published: July 2024

e24103

Background: Due to the contraindication of low-power laser therapy in the tumor region, the use of copaiba for the management of oral mucositis was proposed, given its anti-inflammatory, antimicrobial and healing properties. This study aimed to evaluate the dose-limiting toxicity/maximum tolerated dose of copaiba aqueous mouthwash solution. Methods: This is a phase I study including patients with cavity or oropharynx cancer (CID-10 C00-C06,10), undergoing radiotherapy alone or associated with chemotherapy. Six successive cohorts were proposed, with a minimum of 3 patients each. The copaiba aqueous mouthwash was used daily starting on the first day of radiotherapy and up to 37 days, associated with Low Power Laser applications (100Mw, 660nm, beam area 0.09842 cm²,1J) in non-tumoral areas. In cohorts 1, 2, and 3, a 10% solution was used, and in cohorts 4, 5, and 6, 15%, 2, 3 and 4 times a day, respectively. Daily assessment was carried out evaluating the presence of oral mucositis lesions (World Health Organization and Oral Mucositis Assessment Scale) and complaints of pain (CTCAE v5.0 and Visual Analogue Pain Scale) and xerostomia (presence or absence). Sialometry was carried out through the collection of unstimulated saliva (by Davies (2002) criteria), once a week. Results: Twenty patients were included (cohort 1 = 5, cohort 2 = 3, cohort 3 = 3, cohort 4 = 3, cohort 5 = 3, cohort 6 = 3) - 1 patient was excluded and 1 discontinued from cohort 1 (due to changes in radiotherapy planning and non-adherence to dentistry appointments). A total of 19 participants used the mouthwash. Most of the participants were women (57.9%), with a median age of 63.2 years, and performance status 1 (84.2%). Most tumors were squamous cell carcinomas (84.2%), 47.4% of them in the palate; 57.9% were staged as IVA. Themedian total radiotherapy dose was 68.0 (60.0-70.0) Gy delivered in 33.0 (30.0-34.5) fractions. Pain in the oral cavity (73.7%) and oropharynx (52.6%) were referred, graded respectively as 4.5 (0.75-7) and 1.5 (0-6). Oral mucositis was classified as grade 3 at most; none of the patients developed grade 4 or had to have radiotherapy interrupted due to toxicity. Ulcerated lesions of oral mucositis developed in the tumor area in 68.4% of patients and non-tumor areas in 84.2%. Patients complained of xerostomia in 73.7% of cases and the median unstimulated sialometry was 0.17mL/min. None of the patients experienced dose-limiting toxicity related to the copaiba solution. Conclusions: Copaiba mouthwash did not trigger dose-limiting toxicity in any of the patients throughout the study, leading to amaximum tolerated dose of 15%, 4 times/day. None of the patients complained of pain or burning related to the use of mouthwash in the absence of oral mucositis lesions, suggesting that it is safe and non-toxic for this use. In this sense, considering the obtained results, the development of a phase II study becomes the next logical step in this research area. Clinical trial information: ID - 34635020.5.0000.5274.