Analysis of cytokines in ECOG E4Z02: A phase III randomized study of l-carnitine supplementation for fatigue in patients with cancer

Abstract

9635 Background: The purpose of the study was to investigate associations between fatigue, depression and pain and serum levels of proinflammatory cytokines among pts randomized to l-carnitine supplementation or placebo. Methods: 376 cancer pts with normal hemoglobin and fatigue assessed as moderate or severe were randomized to 4 wks of supplementation with oral carnitine (n=189) or placebo (n=187) 1000 mg bid. Serum levels of 10 inflammatory cytokines and growth factors were measured with Luminex bead ELISA at baseline and 4 wks for 98 pts. Wilcoxon rank sum tests were used to compare cytokine levels between arms and between pts with/without symptoms. Multivariable models of fatigue, depression and pain at 4 wks were examined, adjusting for treatment arm, baseline symptoms and baseline cytokine levels. Results: There were no statistically significant differences in cytokine levels between pts with or without severe fatigue, pain, or depression at baseline. Levels of IL-1rα were higher at baseline among pts randomized to placebo (p=0.01) and increased after 4 wks, while levels among pts randomized to l-carnitine declined (p <0.001). Levels of IFN-γ, TGF-α, IL-6, and TNF-α decreased more among pts randomized to placebo (p=0.008, p=0.006, p=0.01, and p=0.05, respectively). Pts with severe pain at 4 wks had greater declines in levels of EGF, IFN-γ, IL-1α, and IL-1rα than pts without (p=0.05, 0.05, 0.02 and 0.03, respectively). Reductions in IL-1α and TGF-α predicted lower pain severity at 4 wks (p=0.02 and p=0.04, respectively). Conclusions: Levels of proinflammatory cytokines or EGFR ligands failed to distinguish between patients with moderate vs. severe fatigue or levels of depression and pain (severe vs. not) prior to treatment intervention. Lower levels of IL-1α and TGF-α appear to be associated with improvement of pain severity but are not associated with treatment. Mechanisms for these findings require exploration. No significant financial relationships to disclose.