Urinary excretion of prostacyclin and thromboxane degradation products in patients with ovarian malignancy: effect of cytostatic treatment

Abstract

Summary We studied the effect of ovarian cancer and its chemotherapy on the urinary excretion of prostacyclin (PGI2) and thromboxane A2 (TxA2) hydration and metabolic products. In six patients we measured 6-keto-PGF,a and 2,3-dinor-6-keto-PGF,. (PGI2 products) and thromboxane B2 (TxB2) and 2,3-dinor-TxB2 (TxA2 products) by HPLC followed by radioimmunoassay before, during and after the combined infusion of cisplatin, 4'epi-adriamycin and cyclophosphamide. Before the first cytostatic infusion, the urinary excretion of prostanoids was on average 4.4-5.8 times higher than in patients with ovarian endometriosis (n= 19). The infusion of cytostatics led to a 50-120% rise in the excretion of prostanoids during the first post-infusion 9 hours, but in the subsequent 10 hours their ouput was 25-45% below the initial value and remained low for at least 2 weeks. Following repetitive courses of cytostatics (2-4 per patient), prostanoid excretion tended to normalise. These data suggest that ovarian cancer is associated with increased production of PGI2 and TxA2, and that cytostatics suppress this production. This may be of biological significance in tumour behaviour and in the effect of cytostatics.

Chemotherapy-Induced Thrombosis: A Role for Microparticles and Tissue Factor?

“…Mechanisms potentially involved in chemotherapy-associated hypercoagulability can be classified into (a) alterations of tumor cells and tumor cell interactions with host cells, (b) influences on blood cells including the release of cytokines, (c) damage to the vascular endothelium, and (d) interference with components of the plasmatic system. Examples are an upregulation of TF expression in etoposide-, methotrexate-, and vincristine-treated tumor cell lines, 11 an increased human platelet reactivity and TF-associated procoagulant activity of monocytes after cisplatin treatment, [12][13][14] a downregulation of the protein C anticoagulant pathway and an increased adhesion molecule expression on chemotherapy-treated endothelial cells, 15,16 and decreased plasma levels of free activated protein C, protein C, protein S, or antithrombin in patients treated with different chemotherapeutic agents. [17][18][19][20][21] In recent years, fundamental changes in the understanding of hemostasis have taken place due to the observation that thrombus formation might be augmented by high levels of circulating TF and procoagulant MPs.…”