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Original Research

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Adjuvant CMF-chemotherapy and haemostasis. Effect of "classical" and "modified" adjuvant CMF-chemotherapy on blood coagulation fibrinolysis in patients with breast cancer

  • C. Oberhoff1,*,
  • U. H. Winkler2
  • O. Hoffmann1
  • A. E. Schindler1

1Center of Gynecology and Obstetrics, Dept. of Gynecology and Gynecological Oncology, University Hospital Essen, Germany

2Department of Gynecology and Obstetrics, Friedrich-Ebert-Krankenhaus, Neumiinster, Germany

DOI: 10.12892/ejgo200002147 Vol.21,Issue 2,March 2000 pp.147-152

Published: 10 March 2000

*Corresponding Author(s): C. Oberhoff E-mail:

Abstract

Effects of "classical" and "modified" adjuvant CMF-chemotherapy on haemostasis were studied in 22 patients with breast cancer receiving cyclophosphamide (100 mg/m2 p.o.; days 1-14 or 600 mg/m2 i.v.; days 1,8), methotrexate (40 mg/m2 i.v.; days 1,8) and 5-fluorouracil (600 mg/m2 i.v.; days 1,8). Blood collection was done prior to chemotherapy on day 1 and 8. A significant decrease of protein C antigen and activity associated with cumulative effects was observed from day 1 to 8. This effect was similar with "classical" and "modified" CMF-chemotherapy but the reduction of protein C was more pronounced with the oral application of cyclophosphamide. In absence of any significant cumulative decrease of other vitamin K-dependent blood coagulation proteins (factor VII, protein S), the simultaneous decrease of protein C activity and antigen indicates a specific influence of CMF-chemotherapy on vitamin K-dependent protein C-synthesis in the liver.

Keywords

Adjuvant chemotherapy; Breast cancer; Cyclophosphamide; Haemostasis; Protein C; Thrombosis

Cite and Share

C. Oberhoff,U. H. Winkler,O. Hoffmann,A. E. Schindler. Adjuvant CMF-chemotherapy and haemostasis. Effect of "classical" and "modified" adjuvant CMF-chemotherapy on blood coagulation fibrinolysis in patients with breast cancer. European Journal of Gynaecological Oncology. 2000. 21(2);147-152.

References

[1] Bonnadonna G., Brusamolino E., Valagussa P., Rossi A., Bugnatelli L., Brambilla C. et al.: "Combination chemotherapy as an adjuvant treatment in operable breast cancer". N. Engl. J. Med., 1976, 294, 405.

[2] Bonnadonna G., Valagussa P., Moliterni A., Zambetti M., Brambilla Ch.: "Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node positive breast cancer. The results of 20 years follow-up". N. Engl. J. Med., 1995, 332, 901.

[3] Clahsen P. C., van der Velde C. J. H., Julien J. P., Floiras J. L., Mignolet F. Y. et al.:'Thromboembolic compliations after perioperative chemotherapy in women with early breast cancer: A European Organisation for Research and Treatment of Breast Cancer Cooperative Group Study". J. Clin. Oncol., 1994, 12, 1266.

[4] Levine M. N., Gent M., Hirsh J., Arnold A., Goodyear M. D., Hryniuk W. et al.:'The thombogenic effect of anticancer drug therapy in women with Stage II brea、t cancer". N. Engl. J. Med., 1988, 318, 404.

[5] Perloff M., Lesnick G. J., Korzun A., Chun F., Holland J. F., Thrilwell M. P. et al.: "Combination chemotherapy with mastectomy or radiotherapy for stage III breast cancer: A cancer and leukemia group B study". J. Clin. Oncol., 1988, 6, 261.

[6] Saphner T., Tormey D. C., Gray R.: "Venous and arterial thrombosis in patients who received adjuvant therapy for breast cancer" J. Clin. Oncol., 1991, 9, 286.

[7] Pritchard K. I., Paterson A. H. G., Paul N. A., Zee B., Fine S., Pater J. for the National Cancer Institute of Canada Clinical Trials Group Breast Cancer Site Group: "Increased thromboembolic compliations with concurrent tamoxifen and chemotherapy in a randomized trial of adjuvant therapy for women with breast cancer". J. Clin. Oncol., 1996, 14, 2731.

[8] Goodnough L. T., Saito H., Manni A., Jones P. K., Pearson O. H.: "Increased incidence of thromboembolism in Stage IV breast cancer patients treated with a five-drug chemotherapy regime - a study of 159 patients". Cancer, 1984, 54, 1264.

[9] Levine M. L.: "Double-blind randomized trial of very low warfarin for prevention of thromboembolism in stage IV breast cancer". Lancet, 1994, 343, 886.

[10] Cannobio L., Fassio T., Ardizzoni A., Bruzzi P., Querirolo M. A., Zarcone D. et al.: "Hypercoagulable state induced by cytotoxic drugs in stage II breast cancer patients". Cancer, 1986, 58, 1032.

[11] Feffer S. E., Carmosino L. S., Fox R.: "Acquired protein C deficiency in patients with breast cancer receiving cyclophosphamide, methotrexate and 5-fluorouracil". Cancer, 1989, 63, 1303.

[12] Rogers II J. S., Murgo A. J., Fontana J. A., Raich P. C.: "Chemotherapy for breast cancer decreases plasma protein C and protein S". J. Clin. Oncol., 1988, 6, 276.

[13] Rella C., Coviello M., Giotta F., Maiello E., Colavito P., Colangelo D.: "A prothrombotic state in breast cancer patients treated with adjuvant chemotherapy". Breast Cancer Res. Treat., 1996, 50, 73.

[14] Moore M. J.: "Clinical pharmacokinetics of cyclophophamide" Clin. Pharmacokinet., 1991, 20, 194.

[15] Juma F. D., Rogers H. J., Tounce J. R.: "Pharmacokinetics of cyclophosphamide and alkylating activity in man after intravenous and oral administration". Br. J. Clin. Pharmac., 1979, 8, 209.

[16] Engelsman E., Klijn J. C. M., Rubens R. D., Wildiers L Beex L V. A. M., Nooij M. A.: "Classical" CMF versus a 3-weekly intravenous CMF schedule in postmenopausal patients with advanced breast cancer. An EORTC breast cancer co-operative group phase III trial (I 0808)". Eur. J. Cancer, 1991, 27, 966.

[17] Jespersen J., Bertina R. M.: "ECAT Assay Procedures". Haverkate, Kluwer Academic Publishers, 1982.

[18] Kluft C., Verheijen J. H.: "Leiden fibrinolysis working party Blood collection and handling procedures for assessment of tissuetype plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1)". Fibrinolysi'1,1990, 4, Suppl. 2, 155.

[19] Kluft C., Meijer P.: "Update 1996: Blood collection and handling procedures for assessment of plasminogen activators and inhibitors (Leiden Fibrinolysis Workshop)". Fibrinolysis , 1996, 10, Suppl. 2, 171.

[20] SAS Institute Inc.: "SAS User's Guide Statistic". Version 5 Edition. Cary, NC: SAS Inst Inc., 1985.

[21] Aillaud M. F., Roul C., Elias E., Bouvier J. L., Serradimigni, Juhan-Vague I.: "Clinical relevance of plasma fibrin degradation products determination in patients with deep vein thrombosis". Thromb. Haemost., 1987, 58, 332.

[22] Graeff H., Hafter R.: "Detection and relevance of crosslinked fibrin derivates in blood". Semin. Thromb. Haemost., 1982, 8, 57.

[23] McCulloch P., Nieuwenhuizen W., Douglas J., Lowe G. D. O., George W. D.: "Coagulation disturbances in cancer of the breast and colon measured with specific monoclonal antibody enzyme immunoassay for fibrin-fibrinogen degradation products". Hameostasis, 1990, 20, 73.

[24] Esmon C. T.: "Protein C.: Biochemistry, physiology and clinical implications". Blood, 1983, 62, 1155.

[25] Esmon C. T., Owen W. G.: "Identification of an endothelial cell cofactor for thrombin-catalyzed activation of protein C". Proc. Natl. Acad. Sci. USA, 1981, 78, 2249.

[26] Dahlback B.: "The protein C anticoagulant system: Inherited defects as a basis for venous thrombosis". Thromb. Res., 1995, 77, 1.

[27] Finazzi G., Barbui T.: "Different incidence of venous thrombosis in patients with inherited deficiencies of antithrombin III, protein C and protein S". Thromb. Haemost., 1994, 71, 15.

[28] Hyman J., Zimmerman J. H.: "Hepatotoxic effects of oncotherapeutic agents". Prog. Liver. Dis., 1990, 7, 621.

[29] Wooly P. V.: "Hepatic and pancreatic damage produced by cytotoxic drugs". Cancer Treat. Rev., 1983, 10, 117.

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