CYP450 and drug efflux transporters polymorphism influence clinical outcomes of Thai osimertinib-treated non-small cell lung cancer patients

Background: Osimertinib has shown greater efficacy than standard epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and fewer grade 3 or higher adverse drug reactions (ADRs) in patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. However, the clinical outcomes of osimertinib treatment vary depending on the patient’s ethnicity. Therefore, further research is necessary to evaluate the impact of single nucleotide polymorphisms (SNPs) in cytochrome P450 (CYP450) and drug transporters on the therapeutic outcomes and ADRs to osimertinib in Thai patients, to provide improved pharmacological treatments for cancer patients.Methods: This retrospective and prospective cohort study enrolled 63 Thai patients with NSCLC treated with 80 mg of osimertinib once daily as monotherapy. Seventeen SNPs in candidate genes related to drug metabolism and transport pathways were analyzed in each patient. Chi-square or Fisher’s exact tests were used to evaluate the associations between SNPs and clinical outcomes, including ADR incidence and objective response rate (ORR). In addition, the correlation between the genotype and median time to treatment failure (TTF) or progression-free survival (PFS) was assessed using Kaplan-Meier analysis and a log-rank test.Results: We identified six SNPs (rs2231142 and rs2622604 in ABCG2, rs762551 in CYP1A2, rs1057910 in CYP2C9, rs28371759 in CYP3A4, and CYP2A6 deletion polymorphism (CYP2A6*4)) that significantly increased the incidence of ADRs. In addition, we found two SNPs (rs2069514 in CYP1A2 and rs1057910 in CYP2C9) that significantly decreased the median TTF, and two SNPs (rs28399433 in CYP2A6 and rs1057910 in CYP2C9) that significantly decreased the median progression-free survival (PFS). Specifically, we found that one of these SNPs (rs1057910 in CYP2C9) influenced ADRs, TTF, and PFS. Additionally, SNPs in the CYP2A6 heterozygous variant (non4/*4) significantly increased ADR incidence, leading to a high frequency of dose reduction (27.0%).Conclusion: Our study demonstrated significant SNPs associated with increased ADR incidence, decreased PFS, and decreased TTF in Thai patients with NSCLC treated with osimertinib. The CYP2C9 (*3) and CYP2A6 (*4) allele frequencies differed between ethnicities and were associated with an increased incidence of ADRs. These findings highlight the importance of considering genetic factors in NSCLC treatment and may facilitate personalized medicine approaches. Moreover, our study showed a higher incidence of ADRs than the previous trials, including FLAURA and AURA2, and a higher frequency of dose reduction than reported in the AURA 3 trial, possibly due to genetic differences among the study populations

Enteropathogenic Bacterial and Intestinal Parasitic Infections among Asymptomatic Food Handlers in Rangsit University Canteens, Central Thailand

Food handlers play an important role in the transmission of foodborne diseases. 108 asymptomatic food handlers work in RSU canteens and have never been checked for intestinal bacteria and parasites, which might be a potential source of infection for customers. This study is aimed at estimating the prevalence of enteropathogenic bacterial and intestinal parasitic infections among food handlers in Rangsit University canteens, central Thailand. A total of 79 food handlers were enrolled, and each provided one stool sample (response rate of 73.2%). Females comprised 93.7% of study participants, and the largest age group was 41–50 years (34.2%). The prevalence of enteropathogenic bacteria in stool cultures was 2.5%, and only Aeromonas spp. were detected. The pathogenic protozoa Giardia duodenalis was detected in 1.3% of samples, and nonpathogenic protozoa was found in 11.4%. No helminths were found in any samples. Approximately 80% of food handlers demonstrated good hygiene practices, including regular hand washing after visiting the toilet, regular hand washing when preparing food, using soap when washing hands, wearing uniforms/gowns, practicing correct hand washing techniques, and having short fingernails. However, the results showed a lack of personal hygiene training and routine medical care (>50% of samples). Stronger intervention would help to eliminate future infections