Plasma cytokine and P‐selectin levels in advanced malignancy

Abstract

BACKGROUND The survival benefit described in patients with cancer treated with low molecular weight heparin (LMWH) may result from a LMWH‐mediated effect on the immune system or on the cross‐talk between platelets and tumor cells. METHODS Plasma levels of interleukin (IL)‐10, IL‐6, interferon (IFN)‐γ, and P‐selectin were measured in patients with advanced stage malignancy who were randomized to receive standard cancer care with or without the addition of LMWH. RESULTS Patients with IL‐6 levels above the median had a median survival of 6.5 months versus 8.8 months for those with values below this cutoff (P = 0.02). IL‐10 levels were found to be similarly correlated with survival such that IL‐10 concentrations above the detection limit of the assay were associated with a doubled risk of dying in comparison to undetectable IL‐10 (P = 0.02). No significant association was found between survival and circulating levels of IFN‐γ. For P‐selectin, patients with values below the fourth quartile had a median survival of 8.8 months versus 6.5 months for patients with levels above the fourth quartile (P = 0.02). In multivariate analysis, IL‐10 remained an independent unfavorable prognostic factor (hazard ratio, 2.13; 95% confidence interval, 1.08–4.20). In patients treated with LMWH, the plasma levels of IL‐6, IL‐10, IFN‐γ, and P‐selectin demonstrated similar correlations with survival. However, none of the markers was associated with the beneficial survival effects observed with the administration of LMWH. CONCLUSIONS IL‐10, IL‐6, and P‐selectin levels predicted a poor outcome in patients with advanced stage malignancy. The prolongation in survival observed with LMWH in patients with cancer apparently cannot be explained by a LMWH effect on these circulating markers. Cancer 2005. © 2005 American Cancer Society.