BLOOD-COAGULATION DURING ADJUVANT EPIRUBICIN CYCLOPHOSPHAMIDE CHEMOTHERAPY IN PATIENTS WITH PRIMARY OPERABLE BREAST-CANCER/

Purpose: Influences of adjuvant epirubicin/cyclophosphamide (EC) chemo therapy on blood coagulation were investigated in patients with operab le breast cancer and the incidence of thromboembolic events was record ed. Patients and Methods: In 50 consecutive node-positive breast cance r patients, serial coagulation studies (fibrinogen method of Clauss, a ntithrombin III, protein C amidolytic methods, D dimer enzyme-linked i mmunoadsorbent assay [ELISA] techniques, and plasminogen activator inh ibitor [PAI] activity u-PA inhibition test) and impedance plethysmogra phy (IPG) for screening of deep vein thrombosis (DVT) were performed p reoperatively and postoperatively, before each of six cycles of adjuva nt chemotherapy (60 mg/m(2) epirubicin and 600 mg/m(2) cyclophosphamid e) and 3 months thereafter. Seventy-two healthy women served as contro ls. Results: During chemotherapy, the phlebographically proven DVT inc idence was 10% (n = 2 after second cycle; n = 3 after third cycle). Pr eoperative levels of D-dimer, fibrinogen, and the PAI activity were si gnificantly higher than in healthy women and only mean levels of the D -dimer were significantly higher in patients with DVT compared with pa tients without DVT. Postoperatively, only D-dimer and fibrinogen level s significantly increased, while in the course of chemotherapy, these levels were significantly decreased. Mean D-dimer levels and PAI incre ased steadily in patients with DVT. Preoperatively and during chemothe rapy, levels of antithrombin III and protein C were within the normal range. Only one patient with DVT had decreased protein C levels throug hout chemotherapy. Conclusion: Monitoring with sophisticated coagulati on tests during adjuvant EC chemotherapy for breast cancer does not id entify patients at higher risk for DVT development, Preoperatively, in patients with later DVT, an imbalance of hemostasis is already presen t; thus, thrombosis might predominantly be initiated by malignancy-ind uced hypercoagulability and secondarily by the influence of EC chemoth erapy. Prospective randomized trials must determine whether prophylact ic anticoagulation during EC chemotherapy reduces the incidence of DVT . (C) 1996 by American Society of Clinical Oncology.