A PROTHROMBOTIC STATE IN BREAST-CANCER PATIENTS TREATED WITH ADJUVANTCHEMOTHERAPY

Cancer is often associated with abnormal activation of coagulation lea ding to a prothrombotic state. Some chemotherapeutic agents used for c ancer may induce thrombosis but their biological alterations in the he mostatic system are not yet well understood. This study evaluated alte rations of coagulative and fibrinolytic parameters following chemother apy. In plasma samples of 38 patients (median age: 49 years) receiving CMF (schedule 1-21 or 1-8) for Stage II breast cancer, we evaluated: PT, aPTT, antithrombin III (AT-III), protein C (PC), protein S (PS), t hrombin-antithrombin complex (TAT), prothrombin fragment F1+2 (F1+2), fibrinogen (Fbg), tissue-type plasminogen activator (t-PA), plasminoge n activator inhibitor (PAI-1) and D-dimer (D-D). PT, aPTT, and Fbg wer e determined with routine methods; AT-III, PC, and PS were measured wi th coagulative tests; PC and PS were also evaluated with immunoenzymat ic methods. t-PA, PAI-1, D-D, TAT, and F1+2 were measured with immunoe nzymatic methods. All tests were performed immediately before starting therapy and after each cycle. A PC antigen decrease appeared soon aft er beginning therapy and lasted throughout chemotherapy. The lowest va lues were present after the first treatment both in the CMF 1-21 group (mean +/- SD = 72.5 +/- 10.8%) and in the CMF 1-8 group (mean +/- SD = 77.2 +/- 6.9%); PC activity was also decreased. PS antigen decreased after the first administration (mean +/- SD = 73.3 +/- 10% in CMF 1-2 1 group, and 72.5 +/- 4.9% in CMF 1-8 group); PS activity also decreas ed. PAI-1 antigen levels increased (mean +/- SD = 43.1 +/- 20.4 ng/ml in the CMF 1-21 group, and 37.5 +/- 12.2 ng/ml in CMF 1-8 group) lasti ng up to the last cycle. CMF provokes a trend toward hypercoagulabilit y; this effect should be considered when chemotherapy is employed in a dvanced cancer patients at high risk for thrombosis, or in patients wi th other risk factors.