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1.
J Thromb Haemost ; 16(9): 1891-1894, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30027649
3.
J Thromb Haemost ; 16(6): 1069-1077, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29573330

RESUMO

Essentials Cancer patients receiving anticoagulants for venous thromboembolism have an elevated bleeding risk. This secondary analysis of CATCH assessed characteristics of clinically relevant bleeding (CRB). CRB occurs in 15% of cancer patients with thrombosis using therapeutic doses of anticoagulation. After multivariate analysis, risk factors for CRB were age >75 years and intracranial malignancy. SUMMARY: Background Cancer patients with acute venous thromboembolism (VTE) receiving anticoagulant treatment have an increased bleeding risk. Objectives We performed a prespecified secondary analysis of the randomized, open-label, Phase III CATCH trial (NCT01130025) to assess the rate and sites of and the risk factors for clinically relevant bleeding (CRB). Patients/Methods Patients with active cancer and acute, symptomatic VTE received either tinzaparin 175 IU kg-1 once daily or warfarin (target International Normalized Ratio [INR] of 2.0-3.0) for 6 months. Fisher's exact test was used to screen prespecified clinical risk factors; those identified as being significantly associated with an increased risk of CRB then underwent competing risk regression analysis of time to first CRB. Results Among 900 randomized patients, 138 (15.3%) had 180 CRB events. CRB occurred in 60 patients (81 events) in the tinzaparin group and in 78 patients (99 events) in the warfarin group (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.45-0.89). Common bleeding sites were gastrointestinal (36.7%; n = 66), genitourinary (22.8%; n = 41), and nasal (10.0%; n = 18). In multivariate analysis, the risk of CRB increased with age > 75 years (HR 1.83, 95% CI 1.14-2.94) and intracranial malignancy (HR 1.97, 95% CI 1.07-3.62). In the warfarin group, 40.4% of CRB events occurred in patients with with an INR of < 3.0. A lower time in therapeutic range was associated with a higher risk of CRB. Conclusions CRB is a frequent complication in cancer patients with VTE during anticoagulant treatment, and is associated with age > 75 years and intracranial malignancy.


Assuntos
Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Neoplasias/sangue , Tinzaparina/efeitos adversos , Tromboembolia Venosa/tratamento farmacológico , Varfarina/efeitos adversos , Idoso , Anticoagulantes/administração & dosagem , Monitoramento de Medicamentos/métodos , Feminino , Hemorragia/epidemiologia , Humanos , Incidência , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Tinzaparina/administração & dosagem , Resultado do Tratamento , Tromboembolia Venosa/sangue , Tromboembolia Venosa/epidemiologia , Varfarina/administração & dosagem
9.
Br J Cancer ; 111(3): 430-6, 2014 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-24960403

RESUMO

BACKGROUND: Current data suggest that platinum-based combination therapy is the standard first-line treatment for biliary tract cancer. EGFR inhibition has proven beneficial across a number of gastrointestinal malignancies; and has shown specific advantages among KRAS wild-type genetic subtypes of colon cancer. We report the combination of panitumumab with gemcitabine (GEM) and oxaliplatin (OX) as first-line therapy for KRAS wild-type biliary tract cancer. METHODS: Patients with histologically confirmed, previously untreated, unresectable or metastatic KRAS wild-type biliary tract or gallbladder adenocarcinoma with ECOG performance status 0-2 were treated with panitumumab 6 mg kg(-1), GEM 1000 mg m(-2) (10 mg m(-2) min(-1)) and OX 85 mg m(-2) on days 1 and 15 of each 28-day cycle. The primary objective was to determine the objective response rate by RECIST criteria v.1.1. Secondary objectives were to evaluate toxicity, progression-free survival (PFS), and overall survival. RESULTS: Thirty-one patients received at least one cycle of treatment across three institutions, 28 had measurable disease. Response rate was 45% and disease control rate was 90%. Median PFS was 10.6 months (95% CI 5-24 months) and median overall survival 20.3 months (95% CI 9-25 months). The most common grade 3/4 adverse events were anaemia 26%, leukopenia 23%, fatigue 23%, neuropathy 16% and rash 10%. CONCLUSIONS: The combination of gemcitabine, oxaliplatin and panitumumab in KRAS wild type metastatic biliary tract cancer showed encouraging efficacy, additional efforts of genetic stratification and targeted therapy is warranted in biliary tract cancer.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Neoplasias do Sistema Biliar/mortalidade , Neoplasias do Sistema Biliar/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Panitumumabe , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Resultado do Tratamento , Proteínas ras/genética , Gencitabina
12.
J Thromb Haemost ; 11(1): 56-70, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23217107

RESUMO

BACKGROUND: Guidelines addressing the management of venous thromboembolism (VTE) in cancer patients are heterogeneous and their implementation has been suboptimal worldwide. OBJECTIVES: To establish a common international consensus addressing practical, clinically relevant questions in this setting. METHODS: An international consensus working group of experts was set up to develop guidelines according to an evidence-based medicine approach, using the GRADE system. RESULTS: For the initial treatment of established VTE: low-molecular-weight heparin (LMWH) is recommended [1B]; fondaparinux and unfractionated heparin (UFH) can be also used [2D]; thrombolysis may only be considered on a case-by-case basis [Best clinical practice (Guidance)]; vena cava filters (VCF) may be considered if contraindication to anticoagulation or pulmonary embolism recurrence under optimal anticoagulation; periodic reassessment of contraindications to anticoagulation is recommended and anticoagulation should be resumed when safe; VCF are not recommended for primary VTE prophylaxis in cancer patients [Guidance]. For the early maintenance (10 days to 3 months) and long-term (beyond 3 months) treatment of established VTE, LMWH for a minimum of 3 months is preferred over vitamin K antagonists (VKA) [1A]; idraparinux is not recommended [2C]; after 3-6 months, LMWH or VKA continuation should be based on individual evaluation of the benefit-risk ratio, tolerability, patient preference and cancer activity [Guidance]. For the treatment of VTE recurrence in cancer patients under anticoagulation, three options can be considered: (i) switch from VKA to LMWH when treated with VKA; (ii) increase in LMWH dose when treated with LMWH, and (iii) VCF insertion [Guidance]. For the prophylaxis of postoperative VTE in surgical cancer patients, use of LMWH o.d. or low dose of UFH t.i.d. is recommended; pharmacological prophylaxis should be started 12-2 h preoperatively and continued for at least 7-10 days; there are no data allowing conclusion that one type of LMWH is superior to another [1A]; there is no evidence to support fondaparinux as an alternative to LMWH [2C]; use of the highest prophylactic dose of LMWH is recommended [1A]; extended prophylaxis (4 weeks) after major laparotomy may be indicated in cancer patients with a high risk of VTE and low risk of bleeding [2B]; the use of LMWH for VTE prevention in cancer patients undergoing laparoscopic surgery may be recommended as for laparotomy [Guidance]; mechanical methods are not recommended as monotherapy except when pharmacological methods are contraindicated [2C]. For the prophylaxis of VTE in hospitalized medical patients with cancer and reduced mobility, we recommend prophylaxis with LMWH, UFH or fondaparinux [1B]; for children and adults with acute lymphocytic leukemia treated with l-asparaginase, depending on local policy and patient characteristics, prophylaxis may be considered in some patients [Guidance]; in patients receiving chemotherapy, prophylaxis is not recommended routinely [1B]; primary pharmacological prophylaxis of VTE may be indicated in patients with locally advanced or metastatic pancreatic [1B] or lung [2B] cancer treated with chemotherapy and having a low risk of bleeding; in patients treated with thalidomide or lenalidomide combined with steroids and/or chemotherapy, VTE prophylaxis is recommended; in this setting, VKA at low or therapeutic doses, LMWH at prophylactic doses and low-dose aspirin have shown similar effects; however, the efficacy of these regimens remains unclear [2C]. Special situations include brain tumors, severe renal failure (CrCl<30 mL min(-1) ), thrombocytopenia and pregnancy. Guidances are provided in these contexts. CONCLUSIONS: Dissemination and implementation of good clinical practice for the management of VTE, the second cause of death in cancer patients, is a major public health priority.


Assuntos
Fibrinolíticos/uso terapêutico , Neoplasias/complicações , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , Antineoplásicos/uso terapêutico , Benchmarking , Consenso , Comportamento Cooperativo , Medicina Baseada em Evidências , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Cooperação Internacional , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Seleção de Pacientes , Recidiva , Medição de Risco , Fatores de Risco , Terapia Trombolítica , Fatores de Tempo , Resultado do Tratamento , Filtros de Veia Cava , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologia
13.
J Thromb Haemost ; 11(1): 71-80, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23217208

RESUMO

BACKGROUND: Although long-term indwelling central venous catheters (CVCs) may lead to pulmonary embolism (PE) and loss of the CVC, there is lack of consensus on management of CVC-related thrombosis (CRT) in cancer patients and heterogeneity in clinical practices worldwide. OBJECTIVES: To establish common international Good Clinical Practices Guidelines (GCPG) for the management of CRT in cancer patients. METHODS: An international working group of experts was set up to develop GCPG according to an evidence-based medicine approach, using the GRADE system. RESULTS: For the treatment of established CRT in cancer patients, we found no prospective randomized studies, two non-randomized prospective studies and one retrospective study examining the efficacy and safety of low-molecular-weight heparin (LMWH) plus vitamin K antagonists (VKAs). One retrospective study evaluated the benefit of CVC removal and two small retrospective studies were on thrombolytic drugs. For the treatment of symptomatic CRT, anticoagulant treatment (AC) is recommended for a minimum of 3 months; in this setting, LMWHs are suggested. VKAs can also be used, in the absence of direct comparisons of these two types of anticoagulants in this setting [Guidance]. The CVC can be kept in place if it is functional, well-positioned and non-infected and there is good resolution under close surveillance; whether the CVC is kept or removed, no standard approach in terms of AC duration has been established [Guidance]. For the prophylaxis of CRT in cancer patients, we found six randomized studies investigating the efficacy and safety of VKA vs. placebo or no treatment, one on the efficacy and safety of unfractionnated heparin, six on the value of LMWH, one double-blind randomized and one non randomized study on thrombolytic drugs and six meta-analyses of AC and CVC thromboprophylaxis. Type of catheter (open-ended like the Hickman(®) catheter vs. closed-ended catheter with a valve like the Groshong(®) catheter), its position (above, below or at the junction of the superior vena cava and the right atrium) and method of placement may influence the onset of CRT on the basis of six retrospective trials, four prospective non-randomized trials, three randomized trials and one meta-analysis. In light of these data: use of AC for routine prophylaxis of CRT is not recommended [1A]; a CVC should be inserted on the right side, in the jugular vein, and distal extremity of the CVC should be located at the junction of the superior vena cava and the right atrium [1A]. CONCLUSION: Dissemination and implementation of these international GCPG for the prevention and treatment of CRT in cancer patients at each national level is a major public health priority, needing worldwide collaboration.


Assuntos
Antineoplásicos/administração & dosagem , Cateterismo Venoso Central/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Fibrinolíticos/uso terapêutico , Neoplasias/tratamento farmacológico , Trombose Venosa Profunda de Membros Superiores/tratamento farmacológico , Trombose Venosa Profunda de Membros Superiores/prevenção & controle , Benchmarking , Cateterismo Venoso Central/instrumentação , Consenso , Comportamento Cooperativo , Remoção de Dispositivo , Desenho de Equipamento , Medicina Baseada em Evidências , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Cooperação Internacional , Seleção de Pacientes , Medição de Risco , Fatores de Risco , Terapia Trombolítica , Fatores de Tempo , Resultado do Tratamento , Trombose Venosa Profunda de Membros Superiores/diagnóstico , Trombose Venosa Profunda de Membros Superiores/etiologia
14.
Lung Cancer ; 78(3): 253-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23026639

RESUMO

BACKGROUND: The incidence and economic impact of lung cancer-associated venous thromboembolic (VTE) events in a contemporary ambulatory setting is unknown. PATIENTS AND METHODS: We conducted a retrospective cohort analysis utilizing the IMS Patient-Centric database of US healthcare claims and recorded VTE events occurring 3-12 months after chemotherapy initiation. RESULTS: Lung cancer (n=6732) and control (n=17 284) cohorts had 51% women, with a mean age of 64 years. VTE occurred in 13.9% of the lung cancer cohort (odds ratio [OR], 3.15; 95% confidence interval [CI] 2.55, 3.89), and 1.4% of the control cohort (P<0.0001). Charlson Comorbidity Index ≥ 5 (CCI; OR, 2.56; 95% CI 1.02, 6.39; P=0.045), the use of erythropoiesis-stimulating agents (ESAs; OR, 1.63; 95% CI 1.40, 1.89; P<0.0001), and congestive heart failure (CHF; OR, 1.29; 95% CI 1.01, 1.66; P=0.045) were associated with VTE. Bleeding occurred in 22.1% of the lung cancer cohort and 7.0% of the control cohort (P<0.0001). Among lung cancer patients the average total healthcare payment was $84,187 in patients with VTE compared to $56,818 in patients without VTE (P<0.0001). CONCLUSIONS: VTE is common among lung cancer patients receiving chemotherapy and is associated with increased healthcare utilization.


Assuntos
Assistência Ambulatorial/economia , Neoplasias Pulmonares/epidemiologia , Embolia Pulmonar/epidemiologia , Tromboembolia Venosa/epidemiologia , Adulto , Idoso , Assistência Ambulatorial/estatística & dados numéricos , Estudos de Casos e Controles , Comorbidade , Feminino , Gastos em Saúde , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Humanos , Hipertensão/epidemiologia , Incidência , Modelos Logísticos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/economia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Embolia Pulmonar/economia , Embolia Pulmonar/etiologia , Estudos Retrospectivos , Fatores de Risco , Tromboembolia Venosa/economia , Tromboembolia Venosa/etiologia
19.
Ann Oncol ; 20(10): 1619-30, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19561038

RESUMO

Cancer is a frequent finding in patients with thrombosis, and thrombosis is much more prevalent in patients with cancer, with important clinical consequences. Thrombosis is the second most common cause of death in cancer patients. Venous thromboembolism (VTE) in cancer is also associated with a high rate of recurrence, bleeding, a requirement for long-term anticoagulation, and worsened quality of life. Risk factors for cancer-associated VTE include particular cancer types, chemotherapy (with or without antiangiogenic agents), the use of erythropoietin-stimulating agents, the presence of central venous catheters, and surgery. Novel risk factors include platelet and leukocyte counts and tissue factor. A risk model for identifying cancer patients at highest risk for VTE has recently been developed. Anticoagulant therapy is safe and efficacious for prophylaxis and treatment of VTE in patients with cancer. Available anticoagulants include warfarin, heparin, and low-molecular weight heparins (LMWHs). LMWHs represent the preferred therapeutic option for VTE prophylaxis and treatment. Their use may be associated with improved survival in cancer, although this issue requires further study. Despite the significant burden imposed by VTE and the availability of effective anticoagulant therapies, many oncology patients do not receive appropriate VTE prophylaxis as recommended by practice guidelines. Improved adherence to guidelines could substantially reduce morbidity, decrease resource use, enhance quality of life, and improve survival in these patients.


Assuntos
Neoplasias/complicações , Guias de Prática Clínica como Assunto , Editoração , Trombose/tratamento farmacológico , Trombose/prevenção & controle , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Trombose/complicações , Trombose/etiologia , Tromboembolia Venosa/prevenção & controle , Varfarina/uso terapêutico
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