Plasma cytokine and P-selectin levels in advanced malignancy - Prognostic value and impact of low-molecular weight heparin administration

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 oil the cross-talk between platelets and tumor cells. METHODS. Plasma levels of interleukin (IL)-10, IL-6, interferon (IFN)-gamma, 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-gamma. 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-gamma, and P-selectin demonstrated similar correlations with Survival. However, none of the markets 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 ill 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