(ChemotherapyAdvisor) – Thrombocytosis is significantly associated with advanced disease and shorted survival in patients with epithelial ovarian cancer, a study published in February 16 issue of The New England Journal of Medicine reported. These data suggest that “paraneoplastic thrombocytosis may be not simply an epiphenomenon of cancer progression but a contributor to the process,” the investigators stated.

Clinical data on 619 patients were analyzed to test whether an association existed between platelet counts and disease outcomes. Underlying mechanisms were explored using human samples and mouse models of epithelial ovarian cancer and effects of platelets on tumor growth and angiogenesis determined.

Compared to those without thrombocytosis, patients with thrombocytosis had significantly elevated plasma levels of thrombopoietin and interleukin-6. Thrombocytosis was abrogated in tumor-bearing mice by silencing thrombopoietin and interleukin-6 and, in tumor-bearing mice and in patients with epithelial ovarian cancer, anti–interleukin-6 antibody treatment significantly reduced platelet counts.

“These findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplastic thrombocytosis, which fuels tumor growth,” they noted. “In addition, neutralizing interleukin-6 significantly enhanced the therapeutic efficacy of paclitaxel in mouse models of epithelial ovarian cancer.”

Countering paraneoplastic thrombocytosis with the use of direct antiplatelet strategies may provide a valuable therapeutic approach, the investigators concluded. One in three women with ovarian cancer has thrombocytosis and is therefore at risk for thromboembolic complications.

Abstract