ABCC2 Gene Polymorphism and Adverse Reactions to Carboplatin and Paclitaxel Treatment in Non-small Cell Carcinoma Patients

• Published in: Drug safety 2022-10, Vol.45 (10), p.1165-1165
• Main Authors: Sequin, C S, Vasconcelos, P E N S, Fidelis, G F S, Morau, M V, Barbeiro, A S, Zambon, L, Perroud, M W, Pincinato, E C, Moriel, P
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Anemia; Biochemical tests; Cancer therapies; Carboplatin; Chemotherapy; Creatinine; Criteria; Deoxyribonucleic acid; Diarrhea; DNA; Frequency analysis; Gene polymorphism; Genomics; Genotypes; Hematology; Heterozygosity; Hypocalcemia; Hyponatremia; Kidneys; Liver; Lung cancer; Nausea; Non-small cell lung carcinoma; Paclitaxel; Patients; Peripheral blood; Platinum; Polymorphism; Population studies; Small cell lung carcinoma; Smoking; Terminology
• ISSN: 0114-5916; 1179-1942

Introduction: The estimate for each year of the triennium 2020-2022 that will occur 30 thousand lung cancer new cases in Brazil1, which can be classified as: small cell lung cancer (SCLC) and non-small cell lung cancer cells (NSCLC), that corresponds the 85% of the cases2. The main NSCLC treatments are platinum-derived chemotherapeutics, highlighting carboplatin and paclitaxel3, adverse drug reaction (ADRs) may compromise the treatment. ABCC2 gene is involved in molecules of transport, polymorphs in this gene may be related wit ADRs and response compromising the effectiveness of treatment4. Objective: Investigate the prevalence the main ADRs after the first cycle of chemotherapy with Carboplatin and Paclitaxel in patients with NSCLC. Analyze the frequency of polymorphism in the gene ABCC2 (rs717620) in those who had hematological and renal ADRs. Methods: Hematological and biochemical tests were performed before and after 21 days of the first chemotherapy session. Hematological, renal, hepatic and gastrointestinal ADRs was determined using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, criteria. Genomic DNA was extracted and purified from peripheral blood using a Wizard® Genomic DNA Purification Kit (Promega, USA) according to the manufacturer's protocol. The ABCC2 (rs717620) the polymorphisms were studied with Taqman® (Applied Biosystems, CA, USA), determined by rtPCR. Results: A total of 85 patients with NSCLC, treated at Clinics of Hospital Unicamp, the most with an average age of 63 years, men (55%), Caucasians (85%), accentuated smokers (35%), abstainer (35%), with performance status (KPS) at 100% (88%) and with adenocarcinoma (63%). Observed that 72% of patients had an hematological ADRs, grade 1 anemia was the most prevalent. 61% had a grade 1 gastrointestinal ADRs: nausea (25%), vomit (8%) and diarrhea (18%). Hepatic ADRs (59%) grade 1 hepatic ADRs was observed in 59%. Renal ADRs grade 1 was observed in 74%, the most prevalent were: reduced creatinine clearance (28%), Hyponatremia (24%), and Hypocalcemia (18%). In the gene ABCC2, was observed heterozygosity (CT) in 56%, 28% homozygous CC and 15% homozygous TT in the population studied, those with genotype CC had more hematological (54%) and renal (44%) ADRs when compared to the others genotypes, the polymorphism were in the HardyWeinberg equilibrium. Conclusion: Patients in this study has a high prevalence of hematological and renal ADRs. The finding suggests that patients