ADVERSE EVENTS OF TREATMENT IN ADVANCED NON-SMALL CELL LUNG CANCER: CONTRIBUTION OF CLINICAL, GENETIC AND EPIGENETIC FACTORS

• Grant number: 25/13604-9
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2025
• End date: September 30, 2026
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Patricia Moriel
• Grantee: Patricia Moriel
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• City of the host institution: Campinas
• Associated research grant: 23/06280-7 - ADVERSE EVENTS OF TREATMENT IN ADVANCED NON-SMALL CELL LUNG CANCER: CONTRIBUTION OF CLINICAL, GENETIC AND EPIGENETIC FACTORS, AP.R
• Associated scholarship(s): 25/24644-1 - Evaluation of Possible Associations Between Genetic Variants in the ABCB1 Gene and Adverse Reactions in Lung Cancer Patients Treated with Carboplatin and Paclitaxel, BP.IC; 25/24642-9 - Evaluation of possible associations between genetic variants in the CYP3A4 gene and adverse reactions in lung cancer patients treated with gefitinib., BP.IC

Abstract

Two research plans were submitted as part of Scientific Initiation (IC) scholarship applications, with objectives directly aligned with the scope of the Regular FAPESP project currently under my coordination. The titles of the proposed projects are:1. **Evaluation of potential associations between genetic variants in the *CYP3A4* gene and adverse drug reactions in lung cancer patients treated with gefitinib**;2. **Evaluation of potential associations between genetic variants in the *ABCB1* gene and adverse drug reactions in lung cancer patients treated with carboplatin and paclitaxel**.Below is the summary of the main FAPESP project:**Main Project Summary:**Lung carcinoma is the leading cause of cancer-related morbidity and mortality worldwide, with over 2.2 million new cases and an estimated 1.8 million deaths in 2020. The most common type is non-small cell lung cancer (NSCLC). In advanced stages of this malignancy, therapeutic strategies have evolved from empirical chemotherapy to personalized approaches based on the histological and molecular characterization of primary tumors. Despite significant advances in targeted therapies and immunotherapy, platinum-based chemotherapy regimens-such as the combination of carboplatin and paclitaxel-remain widely used. However, the effectiveness of these regimens is often limited by the occurrence of adverse drug reactions (ADRs), among which hematological, renal, and hepatic toxicities are the most prominent. Previous studies have indicated that individual genetic variations, such as single nucleotide variants (SNVs), may influence the occurrence and severity of these ADRs. Similarly, the use of gefitinib-a selective tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR), commonly indicated for patients with activating mutations in this gene-can lead to clinically significant adverse reactions such as diarrhea and skin rash, reported in more than half of the treated cases. The literature highlights the involvement of clinical and genetic factors in the development of these toxicities, with hematologic ADRs being more common among patients treated with carboplatin/paclitaxel and dermatologic reactions predominating in those receiving gefitinib.Given this context, the present study aims to identify clinical and genetic factors associated with adverse reactions induced by carboplatin/paclitaxel and gefitinib in NSCLC patients. This is a prospective observational study, using a consecutive, non-probabilistic sampling strategy, and will include patients grouped according to the therapeutic regimen. In the group treated with carboplatin and paclitaxel (patients without EGFR mutations), peripheral blood samples will be collected before and 20 days after the start of chemotherapy. In the gefitinib group (patients with EGFR mutations), blood collection will take place 30 days after treatment initiation. Clinical and demographic data will be obtained from medical records, and ADRs will be classified according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5, from the National Cancer Institute. The SNV analysis will be conducted using microarray technology with the Infinium Global Diversity Array Enhanced PGx on the iScan system (Illumina). (AU)