Plasma levels of platinum-induced fatty acid [16:4n-3] do not affect response to platinum-based chemotherapy: A pilot study in non-small cell lung cancer patients

Abstract

Pre-clinical studies suggest that 16:4(n-3) in purified form or as a component of fish oil might induce platinum-based chemotherapy resistance. Our aim was to determine plasma total and free 16:4(n-3) before and during platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients supplemented with fish oil or provided standard care, and to explore relationships between plasma 16:4(n-3) levels and tumor response to treatment. In a retrospective, secondary data analysis of a prior clinical trial, plasma from patients with NSCLC (n=21) who underwent platinum-based chemotherapy and were assigned to 2.2g/day of eicosapentaenoic (EPA) plus 1.1g DHA/day as fish oil (FO; n=12) or received no intervention (standard care; SC; n=9). Plasma 16:4(n-3) was quantified as free and esterified (total) fatty acid using HPLC-MS/MS. Plasma 16:4(n-3) levels were evaluated over time in relation to fish oil supplementation and response to platinum-based therapy, and compared with a group of healthy subjects (REF; n=11). Plasma 16:4(n-3) was detected in all samples. The percentage change/day in plasma esterified (total) 16:4(n-3) was higher for FO versus SC group (2.7 versus-1.8%/d, U=20, p=0.02), but change in plasma free 16:4(n-3) was not different between FO and SC. Median plasma free and esterified 16:4(n-3) were similar between responders and non-responders to platinum-based chemotherapy. Total and free plasma 16:4(n-3) fatty acids were similar between NSCLC patients and REF (NSCLC vs REF: total 16:4(n-3): 122.9 vs. 95.2nM and free 16:4(n-3) 23.9 vs. 27.6nM). This first of its kind study that evaluated plasma 16:4(n-3) in NSCLC patients showed that 16:4 (n-3) was elevated during FO supplementation, independent of fish oil supplementation or platinum-based chemotherapy.