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 on 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 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.
Di Nisio
Marcello
M
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. marcellodinisio@hotmail.com
Niers
Tatjana M
TM
Reitsma
Pieter H
PH
Buller
Harry R
HR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D016207:Cytokines / Q000097:blood* / Q000187:drug effects; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality; D019007:P-Selectin / Q000097:blood* / Q000187:drug effects; D011379:Prognosis; D016019:Survival Analysis; D015996:Survival Rate
D014408:Biomarkers, Tumor; D016207:Cytokines; D006495:Heparin, Low-Molecular-Weight; D019007:P-Selectin