L Klotz1, I McNeill, N Fleshner. 1. Department of Surgery, University of Toronto, Sunnybrook Health Science Centre, Ontario, Canada.
Abstract
PURPOSE: This prospective study was designed to determine the safety and efficacy of low dose warfarin in the prophylaxis of thromboembolic disease in patients receiving diethylstilbestrol therapy for advanced prostatic carcinoma. MATERIALS AND METHODS: Patients were stratified to receive 1 mg. warfarin and 3 mg. diethyl-stilbestrol daily (younger than 65 years) or 1 mg. warfarin and 2 mg. diethylstilbestrol daily (older than 65 years). Efficacy of therapy was determined by measuring serum prostate specific antigen (PSA), testosterone and international normalized ratio. Patients were monitored for signs and symptoms of hypercoagulability, bleeding and fluid retention. RESULTS: Of the 32 patients enrolled in the study 6 were lost to followup and 4 died of advanced prostatic disease (2), pneumonia (1) and myocardial infarction (1). Patients were followed for a total of 272 months. Median patient age was 73.5 years. Median pretreatment serum PSA was 95.4 microg./l. with a median pretreatment serum testosterone value of 12.9 nmol./l. After 3 months of therapy the median serum PSA was 1.5 microg./l. with a median serum testosterone value of 0.1 nmol./l. Adverse events were common. In 10 patients (31%) clinically significant proximal deep venous thrombosis developed, 2 (7%) had a myocardial infarction, 2 (7%) had transient ischemic attacks, 1 had new prolonged chest pain and 1 had marked dyspnea due to congestive heart failure. Clotting factor assays performed in a subset of 7 patients demonstrated that factor VII failed to normalize. CONCLUSIONS: The significant thromboembolic toxicity associated with the hypercoagulable state induced by diethylstilbestrol is not reduced by fixed low dose warfarin therapy.
PURPOSE: This prospective study was designed to determine the safety and efficacy of low dose warfarin in the prophylaxis of thromboembolic disease in patients receiving diethylstilbestrol therapy for advanced prostatic carcinoma. MATERIALS AND METHODS:Patients were stratified to receive 1 mg. warfarin and 3 mg. diethyl-stilbestrol daily (younger than 65 years) or 1 mg. warfarin and 2 mg. diethylstilbestrol daily (older than 65 years). Efficacy of therapy was determined by measuring serum prostate specific antigen (PSA), testosterone and international normalized ratio. Patients were monitored for signs and symptoms of hypercoagulability, bleeding and fluid retention. RESULTS: Of the 32 patients enrolled in the study 6 were lost to followup and 4 died of advanced prostatic disease (2), pneumonia (1) and myocardial infarction (1). Patients were followed for a total of 272 months. Median patient age was 73.5 years. Median pretreatment serum PSA was 95.4 microg./l. with a median pretreatment serum testosterone value of 12.9 nmol./l. After 3 months of therapy the median serum PSA was 1.5 microg./l. with a median serum testosterone value of 0.1 nmol./l. Adverse events were common. In 10 patients (31%) clinically significant proximal deep venous thrombosis developed, 2 (7%) had a myocardial infarction, 2 (7%) had transient ischemic attacks, 1 had new prolonged chest pain and 1 had marked dyspnea due to congestive heart failure. Clotting factor assays performed in a subset of 7 patients demonstrated that factor VII failed to normalize. CONCLUSIONS: The significant thromboembolic toxicity associated with the hypercoagulable state induced by diethylstilbestrol is not reduced by fixed low dose warfarin therapy.
Authors: Stephen J McPherson; Shirin Hussain; Preetika Balanathan; Shelley L Hedwards; Birunthi Niranjan; Michael Grant; Upeksha P Chandrasiri; Roxanne Toivanen; Yuzhuo Wang; Renea A Taylor; Gail P Risbridger Journal: Proc Natl Acad Sci U S A Date: 2010-02-01 Impact factor: 11.205