Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients receiving chemotherapy for metastatic breast cancer are at high risk of thromboembolic disease. Long-term oral anticoagulant therapy is needed but increases the risk of haemorrhagic complications. We have assessed the safety and efficacy of warfarin in very low doses as prophylaxis. Women receiving chemotherapy for metastatic breast cancer were randomly assigned either very-low-dose warfarin (152 patients) or placebo (159). The warfarin dose was 1 mg daily for 6 weeks and was then adjusted to maintain the prothrombin time at an international normalised ratio (INR) of 1.3 to 1.9. Study treatment continued until 1 week after the end of chemotherapy. The average daily dose from initiation of titration was 2.6 (SD 1.2) mg for the warfarin group and the mean INR was 1.52. The mean time at risk of thrombosis was 199 (126) days for warfarin-treated patients and 188 (137) days for placebo recipients (p = 0.45). There were 7 thromboembolic events (6 deep-vein thrombosis, 1 pulmonary embolism) in the placebo group and 1 (pulmonary embolism) in the warfarin group, a relative risk reduction of about 85% (p = 0.031). Major bleeding occurred in 2 placebo recipients and 1 warfarin-treated patient. There was no detectable difference in survival between the treatment groups. Very-low-dose warfarin is a safe and effective method for prevention of thromboembolism in patients with metastatic breast cancer who are receiving chemotherapy.
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PMID:Double-blind randomised trial of a very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer. 791 87

Malignancy is a risk factor for thromboembolism and anti-cancer chemotherapy can increase this risk. Prophylaxis of thrombosis with very-low-dose warfarin given concurrently with chemotherapy has a significantly reduced rate of thromboembolism in a randomized trial in women with stage IV breast cancer. In a group of 32 patients randomized in one center (16 subjects on warfarin and 16 on placebo), we have prospectively studied the plasma levels of: 1. Markers of 'in vivo' clotting activation (thrombin-antithrombin complex [TAT], prothrombin fragment 1+2 [F1+2] and D-dimer), 2. Factor VII (FVII), and 3. Natural anticoagulants (protein C [PC] and antithrombin [AT]). The aims of this study were: 1. to examine whether laboratory tests predicted those patients who developed thrombosis, and 2. to evaluate the effect of very-low-dose warfarin on hemostatic variables. The patients' hemostatic parameters were evaluated before entry into the study and after starting chemotherapy +/- prophylaxis, before each course for nine courses. Before-treatment results were compared to those of a sex and age-matched non-cancer control group. There was a significant elevation of plasma levels of TAT (p <0.001), F1+2 (p <0.001), D-dimer (p <0.0001) and FVIIa (p <0.05), as well as an increase of FVII proteolysis (p <0.05), whereas plasma PC and AT concentrations were not different from controls. After starting chemotherapy, markers of clotting activation were progressively lower in the group receiving warfarin prophylaxis compared to the group on placebo. Differences between the groups became statistically significant (p <0.01) after the 4th course of chemotherapy. Deep vein thrombosis occurred in two patients in the placebo arm. The results of this study indicate that before therapy, an hypercoagulable state is present in stage IV breast cancer, and after starting chemotherapy, abnormalities of hypercoagulation markers persist, however they are reduced by very-low-dose-warfarin. None of the laboratory variables could predict thrombosis in the single patient.
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PMID:The effect of very-low-dose warfarin on markers of hypercoagulation in metastatic breast cancer: results from a randomized trial. 945 16

Tumor cell metastasis and thrombosis are the major causes of death in cancer patients. Thrombosis in cancer patients may occur when physiologic antithrombotic systems are defective or when prothrombotic activities defeat normal physiologic antithrombotic mechanisms. Malignancies by themselves may already predispose to a hypercoagulable state in cancer patients. Tumor cells can either directly activate the blood clotting system or indirectly stimulate mononuclear cells to synthesize and express various procoagulants, subsequently leading to prothrombin activation, fibrin formation, and generation of a thrombus. In addition, other comorbid predisposing factors effecting thrombosis in cancer patients have to be considered, including surgery, bed rest, infection, long-term indwelling central venous catheters, anticoagulation, and chemotoxic or steroidal anticancer drugs used in adjuvant or palliative cancer treatment. Reliable information on the incidence of thromboembolism in cancer patients is available for breast cancer; less data have been reported for other malignancies. Chemo- and/or hormone therapy in patients with primary or metastatic breast cancer is associated with an increased thromboembolic risk, although the benefits of treatment far outweigh the risks. The current literature discussing the effect of chemo/hormone therapy on blood clotting factors and the associated risk of thrombosis is reviewed, with emphasis on new developments in the area of tissue-specific SERMs (selective estrogen receptor modulators). SERMs are employed as adjuvant therapy in primary breast cancer and in the palliation of advanced breast cancer and may be clinically useful as potential substitutes for long-term hormone replacement therapy, in the treatment of osteoporosis, and for cancer prevention therapy.
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PMID:Thrombophilic state in breast cancer. 1035 83

Capecitabine can interact with warfarin, resulting in altered coagulation parameters and bleeding. Four cases have been reported. We describe a fifth case with life-threatening interaction between these two drugs. A 67-year-old female with metastatic breast cancer developed hemorrhagic blisters, purpura and ecchymoses. She had been well controlled on long-term warfarin (5 mg/day). Capecitabine was initiated 4.5 weeks prior to the bleeding episode. Laboratory work-up revealed an international normalized ratio of 8.56, partial prothrombin time of 61 seconds and prothrombin time of 5.2%. The coagulation parameters gradually normalized within 4 days following vitamin K administration and discontinuation of capecitabine and warfarin. Careful monitoring of coagulation parameters and proper adjustment of the warfarin dose are required in patients taking warfarin and capecitabine concomitantly.
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PMID:Adverse interaction between capecitabine and warfarin resulting in altered coagulation parameters and bleeding: case report and review of the literature. 1603 30