Intracranial hemorrhage in patients with cancer treated with bevacizumab: the Memorial Sloan-Kettering experience

Khasraw, Mustafa; Holodny, Andrei I.; Goldlust, Samuel; DeAngelis, Lisa M.

doi:10.1093/annonc/mdr148

Cited by 62 publications

(37 citation statements)

References 17 publications

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“…In BEV-treated patients with primary extracranial tumors an ICH rate of 3.7% [12] and of 1-2% in patients with intracerebral metastases [2] was not significantly elevated.…”

Section: Comparable Results Were Observed By Friedman Et Al (Ich-ratmentioning

confidence: 70%

A comprehensive analysis of vascular complications in 3,889 glioma patients from the German Glioma Network

et al. 2012

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Ischemic strokes, intracranial hemorrhages (ICH) and deep venous thromboembolism (DVT) are clinically important events in patients with gliomas. In this multicentre, noninterventional observational study, current data pertaining to frequency, contributing factors and outcomes of vascular events during times of anti-angiogenic therapy with the antibody against vascular endothelial growth factor, bevacizumab (BEV) was collected from the German Glioma Network. Among 3,889 glioma patients, 70 ischemic strokes (1.8 %) and 123 ICH (3.2 %) were recorded. 143 DVT (5.0 %) were recorded in 2,855 patients. Rates of DVT and ICH, but not of ischemic strokes, increased with the World Health Organization (WHO) grade of glioma. In 81 BEV-treated patients, five ischemic strokes (6.2 %), one ICH (1.2 %) and six DVT (7.4 %) were documented. Compared to patients that were not treated with BEV, ischemic stroke rate was significantly higher during treatment with BEV (p < 0.001). The rates of DVT (p = 0.123) or ICH (p = 0.571) in BEV-treated patients did not differ. On cerebral magnetic resonance imaging (MRI), BEV-related ischemic strokes appeared as diffusion-restricted sites next to contrast-enhancing tumor. 67 % of ICH, 61 % of ischemic strokes and 18 % of DVT occurred postoperatively (within 30 days after tumor resection). Outcome after postoperative ICH was significantly worse than after spontaneous ICH (p = 0.008). Ischemic stroke outcomes did not differ between postoperative and spontaneous occurrence (p = 0.401). Rate of pulmonary embolism did not differ significantly between postoperative and spontaneous DVT (p = 0.133). Relatively low rates of ICH and DVT might be partially due to a high proportion of low-grade gliomas in this patient cohort. The finding of a relevant number of symptomatic, therapy-associated intracerebral diffusion restrictions should be controlled in ongoing phase III studies.

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“…In BEV-treated patients with primary extracranial tumors an ICH rate of 3.7% [12] and of 1-2% in patients with intracerebral metastases [2] was not significantly elevated.…”

Section: Comparable Results Were Observed By Friedman Et Al (Ich-ratmentioning

confidence: 70%

A comprehensive analysis of vascular complications in 3,889 glioma patients from the German Glioma Network

et al. 2012

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“…Furthermore, Giantonio et al (16) reported that the incidence of grade 3 or 4 bleeding was higher in patients receiving the FOLFOX4 regimen plus bevacizumab (3.4%) when compared with patients treated with the FOLFOX4 regimen alone (0.4%) or bevacizumab alone (2.1%). In addition, various bleeding locations were reported, including the primary tumor, articular cavities, the eyeball, and encephalic and perinephric spaces (17)(18)(19). The primary tumor was the most common bleeding site, accounting for 2.7% of cases.…”

Section: Discussionmentioning

confidence: 99%

Severe esophageal bleeding in colorectal cancer due to antitumor therapy: A case report

Shen

et al. 2015

Oncology Letters

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Abstract. Colorectal cancer is the third most common type of cancer worldwide, with >1 million cases diagnosed each year. Gastrointestinal bleeding is a common complication of colorectal cancer and is usually associated with the erosion and hemorrhage of the primary tumor. However, in patients who undergo a radical hemicolectomy and do not develop local recurrence, gastrointestinal bleeding may be a result of medical treatments or comorbidities. Esophageal bleeding in such patients is rare. Here, a case of severe esophageal bleeding due to anti-angiogenesis therapy with bevacizumab, and chemotherapy with the FOLFIRI regimen (irinotecan, folinic acid and 5-fluorouracil) in a patient with colorectal cancer is reported, and the possible pathogenesis of this event is analyzed based on the existing literature, in order to provide a reference for such cases.

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“…Patients with brain metastases have been excluded for a long time from clinical trials of bevacizumab because of the risk of bleeding, but the study by Khasraw et al [13], a retrospective analysis to investigate the association between treatment with bevacizumab and intracranial hemorrhage (ICH) in various types of tumors, concluded that bevacizumab does not increase the incidence of ICH in cancer patients. The incidence rates of ICH were 3.6% in patients with brain metastases treated without bevacizumab and 3.9% in patients with brain metastases treated with bevacizumab, and the difference was not statistically significant.…”

Section: Discussionmentioning

confidence: 99%

Bevacizumab-Based Therapy for Patients with Brain Metastases from Non-Small-Cell Lung Cancer: Preliminary Results

et al. 2014

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Background: Bevacizumab is a recombinant humanized monoclonal antibody that obstructs the vascular endothelial growth factor (VEGF) pathway.Despite its extensive employment in the treatment of primary tumors of the brain, experience of brain metastatic disease, a frequent complication in patients with lung cancer, is very limited. On the basis of the strong antiedemigenous effect and no risk of intracranial bleeding, we administered a bevacizumab-based chemotherapy to patients with non-small-cell lung cancer (NSCLC) and symptomatic metastatic brain lesions who were not suitable candidates for a specific local therapy. Methods: The patients received bevacizumab 7.5 mg/kg and cisplatin 75 mg/m² on day 1, and gemcitabine 1,250 mg/m² on days 1 and 8, every 21 days. Results: We studied 13 patients with clinical and radiological progressive brain metastases; the majority had a treatment-naïve disease. Bevacizumab-based chemotherapy was found to be well tolerated and effective: progression-free survival (PFS) was 9.1 months (range: 0.9-39.2+) and overall survival (OS) was 9.6 months (range 3-41.5+). Conclusions: Bevacizumab-based therapy proved to be feasible and safe. The PFS and the OS data are very encouraging as well as the symptomatic benefit due to bevacizumab's high capacity to provide a long-lasting decrease of perilesional edema.

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Intracranial hemorrhage in patients with cancer treated with bevacizumab: the Memorial Sloan-Kettering experience

Abstract: ICH with bevacizumab treatment in this population is rare and does not appear to increase its frequency over the baseline rate of ICH in a comparable population. Most bevacizumab-related ICH occurs into central nervous system tumors but spontaneous hemorrhages were seen.

Cited by 62 publications

References 17 publications

A comprehensive analysis of vascular complications in 3,889 glioma patients from the German Glioma Network

A comprehensive analysis of vascular complications in 3,889 glioma patients from the German Glioma Network

Severe esophageal bleeding in colorectal cancer due to antitumor therapy: A case report

Bevacizumab-Based Therapy for Patients with Brain Metastases from Non-Small-Cell Lung Cancer: Preliminary Results

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