Effects of SLCO1B3, ABCB1 and CYP3A5 polymorphisms on clinical response and adverse events of paclitaxel-based chemotherapy in advanced non-small-cell lung cancer patients

Abstract

Paclitaxel is recommended first-line therapy for patients with advanced non-small cell lung cancer. Genetic polymorphisms of Paclitaxel’s metabolic pathway may affect treatment outcomes and adverse events. The purpose of this study was to determine the association of genetic polymorphisms and clinical outcomes. A total of 58 Thai NSCLC patients with Paclitaxel-based chemotherapy were enrolled for this cohort study. The prevalence of variant allele of SLCO1B3 (rs7311358), ABCB1 (rs2032582) and CYP3A5 (rs776746) were 72.4%, 40.5% and 67.5%, respectively. This study found that SLCO1B3, ABCB1 and CYP3A5 polymorphisms were not associated with clinical response and clinical benefit in paclitaxel-based chemotherapy among Thai advanced NSCLC patients. However, SNPs in ABCB1 were associated with anemia (P=0.025), grade 3 or 4 anemia (P=0.044), and nausea/vomiting (P=0.024). Moreover, SLCO1B3 polymorphisms were significantly associated with grade 3 or 4 anemia (P=0.044) and CYP3A5 polymorphisms associated with grade 3 or 4 peripheral neuropathy (P=0.040). In addition, initial stage and smoking status were significantly associated with neuropathy as P=0.005 and P=0.041, respectively. Nausea and vomiting was associated with smoking status (P=0.024) and gender (P=0.015). And chemotherapy regimen was associated with neutropenia (P=0.039). This study indicated that genetic polymorphism of genes in paclitaxel pathways associated with hematologic and non-hematologic adverse events in Thai advanced NSCLC. These finding might be useful to predict and manage adverse events for NSCLC patient with paclitaxel-based chemotherapy.