Relationship between polymorphisms in the ABCB1 e ABCB2 genes as major toxicities induced by carboplatin and paclitaxel in patients with lung cancer

• Grant number: 20/06703-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2021
• End date: December 31, 2023
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Patricia Moriel
• Grantee: Giovana Fernanda Santos Fidelis
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Lung cancer is the most prevalent type of cancer in Brazil and has the highest mortality rate. One of the treatments used in lung cancer is chemotherapy, which is applied as a palliative treatment in more advanced cases. Among the chemotherapy protocols, the association of carboplatin with paclitaxel is the most indicated combination, but it has several adverse effects, such as myelosuppression. The ABCB1 and ABCB2 genes are involved in the transport of molecules, such as chemotherapeutic agents, and polymorphisms in these genes may be related to drug response and toxicity. Therefore, in order to make treatment more effective and with a lower rate of adverse effects, through a predictive diagnosis, the objective of this study is to relate the polymorphisms in the ABCB1 and ABCB2 genes with the main toxicities induced by carboplatin and paclitaxel in patients with lung cancer in the first cycle of chemotherapy. The study will be conducted at the Hospital das Clínicas of UNICAMP and performed from the blood collection of the patients, upon obtaining the IC (CAAE: 83196318.8.0000.5404). Nephrotoxicity, hepatotoxicity, gastrointestinal toxicities and myelotoxicity, induced by carboplatin, will be investigated and classified according to severity according to the Common Toxicity Criteria (CTCAE - version 4). To determine the polymorphisms in the genes, 4 mL of blood will be collected. DNA isolation will be performed using standardized procedures (Wizard® genomic DNA purification Kit, Promega). The polymorphism research will be carried out by the genotyping system TaqMan® Genotyping Assays (Life Technologies, Foster City, CA) by real-time PCR reaction. Chi-square, Fischer's Exact and Mann-Whitney tests will be used.