The Addition of Bevacizumab to Oxaliplatin-Based Chemotherapy: Impact Upon Hepatic Sinusoidal Injury and Thrombocytopenia

Overman, Michael J.; Ferrarotto, Renata; Raghav, Kanwal; George, Binsah; Qiao, Wei; Machado, Karime Kalil; Saltz, Leonard; Mazard, Thibault; Vauthey, Jean Nicolas; Hoff, Paulo M.; Hobbs, Brian P.; Loyer, Evelyn; Kopetz, Scott

doi:10.1093/jnci/djx288

Cited by 28 publications

(21 citation statements)

References 31 publications

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“…Between potencial risk factors associated to PSVD associated to oxaliplatin, are age, female sex, neurotoxicity, non resecable metastasis, preIQ elevated liver tests and metacronic or sincronic tumor [23]. Additionally, it has been suggested that antiangiogenic factors such as bevacizumab could protect from the development of the liver injury, because it blocks vascular endothelial growth factor (VEGF) [27][28][29]. Studies investigating liver samples from patients who have developed oxaliplatin-induced sinusoidal injury and a preclinical mouse model of sinusoidal injury using monocrotaline have demonstrated upregulation of VEGF-A as a key component of this toxicity [28]; thus, using VEGF tyrosine kinase inhibitors has demonstrated to have a protective effect with regards to monocrotaline-induced sinusoidal obstructive syndrome [25].…”

Section: Oxaliplatin and Liver Damagementioning

confidence: 99%

“…Studies investigating liver samples from patients who have developed oxaliplatin-induced sinusoidal injury and a preclinical mouse model of sinusoidal injury using monocrotaline have demonstrated upregulation of VEGF-A as a key component of this toxicity [28]; thus, using VEGF tyrosine kinase inhibitors has demonstrated to have a protective effect with regards to monocrotaline-induced sinusoidal obstructive syndrome [25]. The protencial protective effect of bevacizumab has been suggested in a recent cohort of more than 200 patients [29].…”

Section: Oxaliplatin and Liver Damagementioning

confidence: 99%

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Porto-Sinusoidal Vascular Disease Associated to Oxaliplatin: An Entity to Think about It

Puente

Fortea

Pozo

et al. 2019

Cells

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Portal sinusoidal vascular disease is a presinusoidal cause of portal hypertension (PHT) of unknown etiology, characterized by typical manifestations of PHT (esophageal varices, ascites, portosystemic collaterals), plaquetopenia and splenomegaly with a gradient of portal pressure slightly increased, according to the presinusoidal nature of the PHT. A few cases in the literature have shown a relationship between oxaliplatin and the development of presinusoidal portal hypertension, years after the chemotherapy for colorectal cancer (therefore, different to sinusoidal obstruction syndrome). There are three mechanisms through which oxaliplatin can cause sinusoidal damage: (1) damage at the level of endothelial cells and stimulates the release of free radicals and depletion of glutathione transferase, with altering the integrity of the sinusoidal cells. The damage in the endothelial sinusoidal cells allows to erythrocytes to across into the Dissé space and formation of perisinusoidal fibrosis, (2) the appearance of nodular regenerative hyperplasia is favored by the chronic hypoxia of the centrilobular areas and, finally, (3) oxaliplatin can generate an obliteration of the blood capillaries and zones of parenchymal extinction. These three facts can develop, in a minority of cases, the appearance of a presinusoidal increase of portal pressure, which typically appears years after the completion of chemotherapy and sometimes is underdiagnosed until variceal bleeding, ascites or encephalopathy appear. The knowledge of this pathology is essential to be able to perform an early diagnostic and consult to the hepatologist.

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Section: Oxaliplatin and Liver Damagementioning

confidence: 99%

Section: Oxaliplatin and Liver Damagementioning

confidence: 99%

Porto-Sinusoidal Vascular Disease Associated to Oxaliplatin: An Entity to Think about It

Puente

Fortea

Pozo

et al. 2019

Cells

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“…Antineoplastics can also lead to chronic and progressive injury, not always apparent from routine biochemistries. For example, oxaliplatin, a drug used to treat colorectal cancer, may cause sinusoid injury and portal hypertension (Overman et al 2018). Oxaliplatin injury can thus mimic clinical signs and symptoms of cirrhosis (varices, enlarges spleen, thrombocytopenia) in the absence of cirrhosis.…”

Section: Antineoplasticsmentioning

confidence: 99%

Drug-Induced Liver Injury in Older Adults

Miller

Abu-Sbeih

Chalasani

2019

Geriatric Gastroenterology

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“…Consequently, human lifespan and life behaviors have undergone tremendous changes. At present, malignant tumors are a critical factor affecting human health and lifespan [1][2][3]. With the increase in the morbidity of malignant tumors, the treatments of malignant tumors are also being explored intensely.…”

Section: Introductionmentioning

confidence: 99%

Clinically Useful and Cost-Effective of Recombinant Human Thrombopoietin in Treatment of Chemotherapy Induced Thrombocytopenia

Wang

Shao

et al. 2020

Preprint

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BackgroundThe bone marrow suppression during chemotherapy will cause severe platelet decline in the human body, resulting in critical organ hemorrhage and intracranial hemorrhage. Therefore, the efficacy and economics of recombinant human thrombopoietin (rhTPO) in treating different degrees of thrombocytopenia caused by chemotherapy were analyzed. MethodsFrom January 2018 to July 2019, 233 with diagnosed lung cancer treated with the course of chemotherapy or chemoradiotherapy were enrolled. After treatment with chemotherapy or chemoradiotherapy, they all happened thrombocytopenia and received rhTPO. We divided patients into three groups according to the level of platelet decline. Changes in blood platelet count, treatment plan and cost performance between them were analyzed. ResultsOf all the included patients, 39.5% was undergoing concurrent radiotherapy or chemotherapy; 42.9% had thrombocytopenia of grade II; 40.3% had thrombocytopenia of grade III; 16.7% had thrombocytopenia of grade IV; 52.8% postponed the next cycle of chemotherapy or radiotherapy due to platelet decline; 12.0% changed the treatment plan for malignant tumors due to severe platelet decline; 15.5% reduced the dose of chemotherapy drugs due to thrombocytopenia; 23.6% had platelet transfusions during this period. During the extended hospitalization period caused by thrombocytopenia, the medical expenses of patients would increase significantly, which was dominated by the cost of rhTPO. ConclusionsFor different degrees of thrombocytopenia, the treatment of rhTPO could increase platelet counts effectively. During the treatment, patients might have varying degrees of economic and the difference between the treatment duration of different patients.

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The Addition of Bevacizumab to Oxaliplatin-Based Chemotherapy: Impact Upon Hepatic Sinusoidal Injury and Thrombocytopenia

Abstract: In metastatic CRC, the addition of bevacizumab to oxaliplatin-based chemotherapy reduces the frequency of splenic enlargement and the rate of thrombocytopenia.

Cited by 28 publications

References 31 publications

Porto-Sinusoidal Vascular Disease Associated to Oxaliplatin: An Entity to Think about It

Porto-Sinusoidal Vascular Disease Associated to Oxaliplatin: An Entity to Think about It

Drug-Induced Liver Injury in Older Adults

Clinically Useful and Cost-Effective of Recombinant Human Thrombopoietin in Treatment of Chemotherapy Induced Thrombocytopenia

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