Effects of Topical Application of Silver-Nimesulide Complex in the Treatment of Patients with Skin Squamous Cell Carcinoma: Phase I/II Study

• Grant number: 24/16361-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2025
• End date: June 30, 2028
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Carmen Silvia Passos Lima
• Grantee: Gisele Goulart da Silva
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 21/10265-8 - Cancer Theranostics Innovation Center (CancerThera), AP.CEPID

Abstract

Introduction: Non-melanoma skin cancer (NMSC) is the most common tumor in Brazil and worldwide, and squamous cell carcinoma of the skin (SSCC) is a common type of NMSC. The conventional treatment for patients with SSCC is surgical resection of the tumor, which can cause physical deformities and functional changes. The results of intravenous administration of cisplatin to patients with SSCC are limited and the adverse effects are considerable. The target-specific agent cetuximab and the immunotherapy agent cemiplimab can be used to treat patients with SSCC, but only part of them respond to the drugs, resistance emerges over time and their costs are high. Topical use of 5-fluorouracil has satisfactory efficacy, but local adverse effects are common and its availability on the global market is limited. Therefore, new therapeutic approaches are required for tumor carriers. Preclinical studies conducted by our group showed antitumor activity of the silver-nimesulide complex, the Ag-NMS, against SSCC in in vitro experiments, and antitumor activity without toxicity of the Ag-NMS complex incorporated into the bacterial cellulose membrane, the BC-Ag-NMS, against SSCC in in vivo experiments.Objectives: To evaluate the safety, efficacy, and mechanism of action of BC-Ag-NMS in patients with SSCC through phase I/II clinical study, aiming to obtain an innovative therapeutic approach. Patients and Methods: The synthesis, characterization and stability of the Ag-NMS and the CB-Ag-NMS, and the evaluation of the retention and release capacity of Ag-NMS by BC-Ag-NMS will be evaluated using conventional procedures. Six patients with CCEP will be evaluated in phase I (treatment toxicity) and twenty patients with CCEP in phase II (treatment efficacy) of the study. Patients will be treated with topical application of BC-Ag-NMS for 21 days and will only be observed for an additional 21 days. Local toxicity and systemic toxicity (hematological examination, liver and kidney function tests, electrolytes) will be evaluated before and after treatment with BC-Ag-NMS. At the end of the observation period, patients will undergo surgical resection of the tumor. Markers of cellular (Ki-67) and vascular (CD34) proliferation, tumor cell apoptosis (Tunel assay) and tumor fibrosis (Masson's trichrome) will be evaluated in histological sections of the tumor and non-targeted (Nanostring) and targeted molecular investigations (quantitative polymerase chain reaction, qPCR) will be evaluated on fresh tumor fragments, obtained before and after treatment with BC-Ag-NMS, aiming to identify the mechanisms of action of Ag-NMS on SSCC. We believe that BC-Ag-NMS can be a safe and effective topical alternative for the treatment of SSCC, minimizing the adverse effects and costs of systemic treatment. The transition to clinical studies in humans, object of the study, is essential to validate these results and bring the product to the market. (AU)