Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(15)01088-0.pdf

Antiangiogenic therapy in oncology: current status and future directions.

EASL Clinical Practice Guidelines : Vascular diseases of the liver European Association for the Study of the Liver

Vascular disorders of the liver, although affecting less than 5/10,000 patients, collectively account for a number of rare conditions that represent an important health problem worldwide in the field of liver diseases. A common characteristic of most of these disorders is that they can cause non-cirrhotic portal hypertension with an ensuing high morbidity and mortality. In addition, special relevance addresses the fact that patients are usually young with an otherwise normal life expectancy that may be markedly shortened if they are not adequately managed. Advances in the knowledge of vascular liver disorders are hampered by the small number of cases and a limited number of studies assessing natural history, pathophysiology or therapy. However, in recent years, interest for these disorders has increased as reflected in the rise in the number of publications on this topic. In addition, EASL has encouraged this increased interest by sponsoring a monothematic conference in June 2012 in Tallinn on vascular disorders of the liver, and by proposing an EASL clinical practice guidelines on the issue. These guidelines will not cover all possible vascular disorders of the liver but are mainly based on the subjects discussed during the monothematic conference; Budd-Chiari syndrome, non-cirrhotic portal vein thrombosis, idiopathic portal hypertension, sinusoidal obstruction syndrome, hepatic vascular malformations in hereditary haemorrhagic telangiectasia and portal vein thrombosis in cirrhosis. Guidelines have been written according to published studies retrieved from Pubmed. The evidence and recommendations have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system. The strength of evidence has been classified into three levels: high (A), moderate (B) or low quality (C), while the grade of recommendation in two levels: strong (1) or weak (2) (Table 1). The higher the quality of the evidence, the more likely a strong recommendation is warranted. Where no clear evidence existed, recommendations were based on agreed opinions of the writing committee members.

https://www.journal-of-hepatology.eu/article/S0168-8278(15)00547-4/pdf

EASL Clinical Practice Guidelines: Vascular diseases of the liver q

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.31646

Vascular Liver Disorders, Portal Vein Thrombosis, and Procedural Bleeding in Patients With Liver Disease: 2020 Practice Guidance by the American Association for the Study of Liver Diseases.

Context The only treatment available to restore normal cardiac output in patients with hereditary hemorrhagic telangiectasia (HHT) and cardiac failure is liver transplant. Anti–vascular endothelial growth factor treatments such as bevacizumab may be an effective treatment. Objectives To test the efficacy of bevacizumab in reducing high cardiac output in severe hepatic forms of HHT and to assess improvement in epistaxis duration and quality of life. Design, Setting, and Patients Single-center, phase 2 trial with national recruitment from the French HHT Network. Patients were 18 to 70 years old and had confirmed HHT, severe liver involvement, and a high cardiac index related to HHT. Intervention Bevacizumab, 5 mg per kg, every 14 days for a total of 6 injections. The total duration of the treatment was 2.5 months; patients were followed up for 6 months after the beginning of the treatment. Main Outcome Measure Decrease in cardiac output at 3 months after the first injection, evaluated by echocardiography. Results A total of 25 patients were included between March 2009 and November 2010. Of the 24 patients who had echocardiograms available for reread, there was a response in 20 of 24 patients with normalization of cardiac index (complete response [CR]) in 3 of 24, partial response (PR) in 17 of 24, and no response in 4 cases. Median cardiac index at beginning of the treatment was 5.05 L/min/m 2 (range, 4.1-6.2) and significantly decreased at 3 months after the beginning of the treatment with a median cardiac index of 4.2 L/min/m 2 (range, 2.9-5.2; P  2 ; range, 3.0-5.1). Among 23 patients with available data at 6 months, we observed CR in 5 cases, PR in 15 cases, and no response in 3 cases. Mean duration of epistaxis, which was 221 minutes per month (range, 0-947) at inclusion, had significantly decreased at 3 months (134 minutes; range, 0-656) and 6 months (43 minutes; range, 0-310) (P = .008). Quality of life had significantly improved. The most severe adverse events were 2 cases of grade 3 systemic hypertension, which were successfully treated. Conclusion In this preliminary study of patients with HHT associated with severe hepatic vascular malformations and high cardiac output, administration of bevacizumab was associated with a decrease in cardiac output and reduced duration and number of episodes of epistaxis. Trial Registration clinicaltrials.gov Identifier: NCT00843440

https://jamanetwork.com/journals/jama/articlepdf/1105048/jpc25002_948_955.pdf

Bevacizumab in Patients With Hereditary Hemorrhagic Telangiectasia and Severe Hepatic Vascular Malformations and High Cardiac Output

Pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia: a series of 126 patients.

Hereditary hemorrhagic telangiectasia (HHT), a genetic vascular disorder associated with epistaxis and hepatic shunts, is responsible for high-output cardiac failure in rare cases Bevacizumab, which targets vascular endothelial growth factor, was shown to decrease both cardiac index (CI) and epistaxis duration in HHT patients with severe liver involvement The relationship between its serum concentration and change in both CI and epistaxis duration was investigated to design the bevacizumab maintenance dosing regimen of future therapeutic studies Twenty-five HHT patients with dyspnea and high CI were included in a prospective non-comparative study They received bevacizumab at a dose of 5 mg/kg per infusion every 14 days for a total of 6 injections The relationships between bevacizumab serum concentration and both CI and epistaxis duration were described using transit compartments and direct inhibition pharmacokinetic-pharmacodynamic models The performances of different maintenance regimens were evaluated using simulation Infusions every 3, 2 and one months were predicted to maintain 41%, 45% and 50% of patients with CI <4 L/min/m(2) at 24 months, respectively The fraction of patients with <20 min epistaxis per month was predicted to be 34%, 43% and 60%, with infusion every 3, 2 or one months, respectively Simulations of the effects of different maintenance dosing regimens predict that monthly 5 mg/kg infusions of bevacizumab should allow sustained control of both cardiac index and epistaxis

Dose – response relationship of bevacizumab in hereditary hemorrhagic telangiectasia

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Bevacizumab in Patients With Hereditary Hemorrhagic Telangiectasia and Severe Hepatic Vascular Malformations and High Cardiac Output

Pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia: a series of 126 patients.

Dose – response relationship of bevacizumab in hereditary hemorrhagic telangiectasia