EVALUATION OF A POSSIBLE ASSOCIATION OF CYP2C8 POLYMORPHISMS WITH ADVERSE REACTIONS IN PATIENTS WITH GYNECOLOGICAL TUMORS TREATED WITH PACLITAXEL AND CARBOPLATIN

• Grant number: 23/02703-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2023
• End date: December 31, 2024
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Patricia Moriel
• Grantee: Yasmim Gabriele Matos
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Gynecological tumors correspond to the group of neoplasms that affect the female reproductive system, and represent one of the main cancers that affect women worldwide. The pharmacological scheme most indicated in advanced stages is the combination of platinum derivative and taxane, which, despite showing good results, still has limitations due to the frequent occurrence of adverse reactions, mainly peripheral neuropathies and hematotoxicity. These events can be attributed to paclitaxel, a chemotherapy drug metabolized by the CYP2C8 enzyme, whose genetic variants have demonstrated relevance in the face of toxicity during treatment. The aim of this study will be to investigate the possible relationship between CYP2C8 gene polymorphisms and the occurrence of adverse reactions in patients with gynecological malignancies treated with paclitaxel and carboplatin. Patients diagnosed with gynecological cancer (ovarian, cervical, endometrial and vulvar cancer), at any clinical stage, who received treatment based on paclitaxel (175 mg/m²) and carboplatin (AUC 5-6) will be included. Genomic DNA samples will be isolated from peripheral blood leukocytes and polymorphisms will be determined using Real Time Polymerase Chain Reaction (qPCR). Adverse events will be evaluated according to the Common Toxicity Criteria (CTCAE). The Hardy-Weinberg balance will be evaluated by the chi-square test. Comparison of allele frequencies will be evaluated using Fisher's exact test and the significance level adopted in all analyzes will be 5% (p<0.05).