136P - Drug transporter pharmacogenetics as a predictor of chemotherapy-induced toxicity in lung cancer patients

Abstract

Background: Lung cancer remains the commonest cancer and the most common cause of cancer-associated death worldwide. Use of chemotherapeutic drugs are significant in managing patients with lung cancer, however, due to serious adverse drug reactions (ADRs) these drugs are often underutilized. Our aim was to perform a meta-analysis and systematic review of studies looking at pharmacogenetic drug transporter variants as predictors of ADRs in lung cancer patients undergoing chemotherapy. Methods: Papers were sourced from Medline, Cochrane Library, CINHL, EMBASE, Web of Knowledge and Scopus. The Cochrane Collaboration Risk of Bias Tool v13 was used to evaluate six types of bias domains for each of the publications reviewed. Where applicable, random effect meta-analysis was used and funnel plots displayed. Results: We report findings on the ATP-binding cassette superfamily (ABC) members ABCB1, ABCC1, ABCC2, ABCG2, ABCA1, ABCC4 and ABCC5. For influx transporters, findings for the solute carrier organic anion transporter family (SLC, SLCO) SLC29A1, SLC2A3, SLC31A1, SLCO1B1 and SLCO1B3 are included. Significant increased risk of irinotecan-induced neutropenia was noted in NSCLC patients expressing ABCB1 2677G>T/G (P = 0.002) or ABCC2 3972T>T (P = 0.04). ABCG2 421C>A was associated with a significant 2-fold increased risk of gefitinib-induced skin toxicity (P = 0.0009). East-Asian patients treated with irinotecan and expressing the SLCO1B1 -1118G>A variant had a 2 -3 fold significant increased risk of diarrhea and neutropenia (P < 0.05). American patients expressing the SLC19A1 IVS2(4935)G>A variant were associated with pemetrexed/gemcitabine induced grade 3+ leukopenia. Conclusions: Whilst current data shows promise regarding ABCB1, ABCC2, ABCG2, SLCO1B1 and SLC19A1 pharmacogenetics, many more studies are required that incorporate larger patient numbers and designed to minimize bias before we can begin to utilizes these variants to optimize chemotherapeutic treatment. Legal entity responsible for the study: Zoulikha Zair Funding: Has not received any funding Disclosure: All authors have declared no conflicts of interest.