rivaroxaban and Pancreatic-Neoplasms

Pancreatic cancer patients are at risk for venous thromboembolism (VTE); the value of thromboprophylaxis has not been definitively established.. This trial randomized cancer patients initiating a new regimen and at high risk for VTE (Khorana score ≥2) to rivaroxaban 10 mg or placebo up to day 180. This analysis examined the subset of pancreatic cancer patients. The primary efficacy endpoint was the composite of symptomatic deep-vein thrombosis (DVT), asymptomatic proximal DVT, any pulmonary embolism, and VTE-related death. The primary safety endpoint was International Society on Thrombosis and Haemostasis-defined major bleeding.. In total, 49/1080 (4.5%) patients enrolled had baseline VTE on screening, with higher rates (24/362 [6.6%]) in pancreatic cancer and they were not randomized. Of 841 randomized patients, 273 (32.5%) had pancreatic cancer; 155/273 (57% in each arm) completed the double-blind period. The primary endpoint occurred in 13/135 (9.6%) patients in the rivaroxaban group and in 18/138 (13.0%) in the placebo group (hazard ratio [HR] = 0.70; 95% CI, 0.34-1.43; P = .328) in up-to-day-180 period and 5/135 (3.7%) patients receiving rivaroxaban and 14/138 (10.1%) receiving placebo in the intervention period (HR = 0.35; 95% CI, 0.13-0.97; P = .034). Major bleeding was similar (2 [1.5%] receiving rivaroxaban and 3 [2.3%] receiving placebo). Correlative biomarker studies demonstrated significant decline in D-dimer (weeks 8 and 16) in patients randomized to rivaroxaban compared to placebo (P < .01).. In ambulatory pancreatic cancer patients, rivaroxaban did not result in significantly lower incidence of VTE or VTE-related death in the 180-day period. During the intervention period, however, rivaroxaban substantially reduced VTE without increasing major bleeding, suggesting benefit of rivaroxaban prophylaxis in this setting.. ClinicalTrials.gov identifier, NCT02555878.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Double-Blind Method; Female; Fibrin Fibrinogen Degradation Products; Hemorrhage; Humans; Incidence; Male; Middle Aged; Outpatients; Pancreatic Neoplasms; Placebos; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism

To compare the bleeding risk in patients with gastrointestinal (GI) cancer with that in patients with non-GI cancer treated with anticoagulation for acute cancer-associated venous thromboembolism (Ca-VTE).. Consecutive patients with Ca-VTE seen at the Mayo Thrombophilia Clinic between March 1, 2013, and April 20, 2020, were observed prospectively to assess major bleeding and clinically relevant nonmajor bleeding (CRNMB).. In the group of 1392 patients with Ca-VTE, 499 (35.8%) had GI cancer including 272 with luminal GI cancer (lower GI, 208; upper GI, 64), 176 with pancreatic cancer, and 51 with hepatobiliary cancer. The rate of major bleeding and CRNMB in patients with GI cancer was similar to that in 893 (64.2%) patients with non-GI cancer treated with apixaban, rivaroxaban, or enoxaparin. Apixaban had a higher rate of major bleeding in luminal GI cancer compared with the non-GI cancer group (15.59 vs 3.26 per 100 person-years; P=.004) and compared with enoxaparin in patients with luminal GI cancer (15.59 vs 3.17; P=.04). Apixaban had a lower rate of CRNMB compared with rivaroxaban in patients with GI cancer (3.83 vs 9.40 per 100 person-years; P=.03). Patients treated with rivaroxaban in the luminal GI cancer group had a major bleeding rate similar to that of patients with non-GI cancer (2.04 vs 4.91 per 100 person-years; P=.37).. Apixaban has a higher rate of major bleeding in patients with luminal GI cancer compared with patients with non-GI cancer and compared with enoxaparin in patients with luminal GI cancer. Rivaroxaban shows no increased risk of major bleeding in patients with GI cancer or luminal GI cancer compared with patients with non-GI cancer.. ClinicalTrials.gov identifier: NCT03504007.

Topics: Enoxaparin; Factor Xa Inhibitors; Female; Gastrointestinal Neoplasms; Hemorrhage; Humans; Liver Neoplasms; Male; Middle Aged; Outcome and Process Assessment, Health Care; Pancreatic Neoplasms; Prospective Studies; Pulmonary Embolism; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Severity of Illness Index; United States; Venous Thrombosis

Some clinical studies have shown that low-molecular-weight heparins (LMWHs) prolong the survival of cancer patients. In addition, various anticoagulants have been shown to reduce growth of tumors in mice. However, there are no studies on the effect of the factor Xa inhibitor rivaroxaban on growth of human pancreatic tumors in nude mice.. To test the hypothesis that the factor Xa inhibitor rivaroxaban reduces the growth of tissue factor (TF)-positive pancreatic tumors but not TF-negative pancreatic tumors in mice.. Rivaroxaban significantly prolonged prothrombin time in tumor-bearing mice. Rivaroxaban did not affect cell proliferation or growth of either BxPc-3 or MIA PaCa-2 tumors grown subcutaneously in nude mice.. Our results indicate that inhibition of factor Xa with rivaroxaban does not affect the growth of two human pancreatic tumors in nude mice.

Topics: Animals; Blood Coagulation; Cell Line, Tumor; Cell Proliferation; Factor Xa Inhibitors; Humans; Male; Mice, Nude; Pancreatic Neoplasms; Prothrombin; Rivaroxaban; Time Factors; Tumor Burden; Xenograft Model Antitumor Assays

Low-molecular-weight heparin (LMWH) is the standard treatment for venous thromboembolism (VTE) in patients with active cancer. However, use of factor Xa inhibitors, such as rivaroxaban, is increasing on the basis of limited clinical evidence. The present single-center study compared the incidence of bleeding and other treatment outcomes in gastrointestinal and pancreatobiliary cancer (GI tract cancer) patients administered rivaroxaban or LMWH for the treatment of VTE.. Retrospective data from 281 GI tract cancer patients who were treated for VTE with rivaroxaban (n = 78) or LMWH (n = 203) between 1 January 2012 and 31 December 2016, were analyzed. Primary end-point was the incidence of major and clinically relevant bleeding. Secondary outcomes included the incidence of recurrent VTE and mortality.. Clinically relevant bleeding occurred in 19 patients (24.4%) in the rivaroxaban group and 31 (15.3%) in the LMWH group (. Compared to LMWH, rivaroxaban was associated with a higher incidence of clinically relevant bleeding in GI tract cancer patients presenting with VTE.

Topics: Anticoagulants; Biliary Tract; Factor Xa Inhibitors; Female; Gastrointestinal Tract; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Pancreatic Neoplasms; Retrospective Studies; Rivaroxaban; Stomach Neoplasms; Venous Thromboembolism

The activation of protease-activated receptor (PAR)-2 by factor Xa (fXa) promotes the release of tissue factor-positive microvesicles (TF

Topics: Adenocarcinoma; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell-Derived Microparticles; Factor VIIa; Factor Xa Inhibitors; Female; Humans; Pancreatic Neoplasms; Pyrazoles; Pyridones; Receptor, PAR-2; Rivaroxaban; Signal Transduction; Thromboplastin

Topics: Administration, Oral; Aged; Anticoagulants; Endocarditis, Non-Infective; Female; Heparin; Humans; Pancreatic Neoplasms; Rivaroxaban; Thrombosis