Effects on blood coagulation of adjuvant CNF (Cyclophosphamide, Novantrone, 5-Fluorouracil) chemotherapy in stage II breast cancer patients

The prospectively studied the alterations of coagulation during adjuvant CN F (Cyclophosphamide, Novantrone - Mitoxantrone, 5-Fluorouracil) chemotherap y in patients with stage II breast cancel: In 50 consecutive stage II breas t cancer patients (pre-peri-postmenopausal), and 50 controls, serial coagul ation parameters including prothrombin time (P.T.), partial thromboplastin time (P.T.T.), fibrinogen, fibrinogen/fibrin degradation products (F.D.P.), protein C, protein S, antithrombin III (AT-III) and platelet count were pe rformed. Blood samples for coagulation tests were collected at pretherapy, midtherapy (before the 3rd course), before the 6(th) course of chemotherapy , and 2 months after the cessation of therapy (post-therapy) of 6 cycles of adjuvant chemotherapy (Cyclophosphamide 500 mg/m(2), Novantrone 10 mg/m(2) 5-Fluorouracil 500 mg/m(2)). Chemotherapy was repeated every 3 weeks. None of our stage II breast cancer patients receiving adjuvant CNF chemotherapy developed thromboembolic complications. Before any treatment all the teste d coagulation parameters were within the normal limits as compared to contr ols. No statistically significant changes of FDP were noted throughout the study. Fibrinogen, plasma protein C, protein S and AT-III were significantl y decreased during chemotherapy. This decline was more evident at midtherap y. Their levels returned to the pretherapy values 2 months after the comple tion of chemotherapy. The P.T was statistically shortened, while the P.T.T. showed a statistically significant prolongation during chemotherapy. In co nclusion, it appears that monitoring stage II breast cancer with sophistica ted coagulation tests during adjuvant CNF chemotherapy can not identify pat ients at high risk for thromboembolic events. These serially performed coag ulation tests, could be considered as a cost-intensive monitoring and not j ustifiable as a screening for breast cancer patients receiving adjuvant che motherapy. However, the increasing number of reports of life-threatening an d sometimes fatal thromboembolic events following chemotherapy ol hormonoch emotherapy are of great concern. Our results suggest caution when using che motherapeutic agents in patients with other thrombosis risk factors, since a significant decrease of protein C and protein S was observed in all patie nts. Additional studies are required to determine the exact association bet ween chemotherapy and/or hormonochemotherapy and thrombotic events.