Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab.

Genentech, Inc., BioOncology, 455 East Grand Ave, South San Francisco, CA 94080, USA.
CancerSpectrum Knowledge Environment (Impact Factor: 14.07). 08/2007; 99(16):1232-9. DOI: 10.1093/jnci/djm086
Source: PubMed

ABSTRACT Although combination treatment with bevacizumab (humanized monoclonal antibody against vascular endothelial growth factor) and chemotherapy improves survival of patients with various metastatic carcinomas, an increased risk of arterial thromboembolic events has been observed in some trials. We characterized this risk by performing post hoc analyses of randomized controlled trials that evaluated combination treatment with bevacizumab and chemotherapy versus chemotherapy alone. Low-dose aspirin was permitted in these trials, and its safety was also analyzed.
Data were pooled from five randomized controlled trials that included a total of 1745 patients with metastatic colorectal, breast, or non-small-cell lung carcinoma. The risk of an arterial or venous thromboembolic event was assessed by simple incidence rates, rates per 100 person-years, and/or hazard ratios (HRs). The association between patient characteristics and risk of an arterial thromboembolic event was investigated primarily by Cox proportional hazards regression. The relationship between low-dose aspirin and bleeding was explored by incidence rates and rates per 100 person-years.
Combined treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was associated with increased risk for an arterial thromboembolic event (HR = 2.0, 95% confidence interval [CI] = 1.05 to 3.75; P = .031) but not for a venous thromboembolic event (HR = 0.89, 95% CI = 0.66 to 1.20; P = .44). The absolute rate of developing an arterial thromboembolism was 5.5 events per 100 person-years for those receiving combination therapy and 3.1 events per 100 person-years for those receiving chemotherapy alone (ratio = 1.8, 95% CI = 0.94 to 3.33; P = .076). Development of an arterial thromboembolic event was associated with a prior arterial thromboembolic event (P<.001) or age of 65 years or older (P = .01). Baseline or on-study aspirin use was associated with modest increases in grade 3 and 4 bleeding events in both treatment groups, from 3.6% to 4.7% for bevacizumab-treated patients and from 1.7% to 2.2% for control subjects.
Combination treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was associated with an increased risk of arterial thromboembolism but not venous thromboembolism.

1 Bookmark
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The current study describes the fibrinolytic treatment of a patient exhibiting an acute massive pulmonary thromboembolism, who was also receiving a bevacizumab-based combination regimen for metastatic colon cancer. The administration of bevacizumab has been associated with an increased risk of venous thromboembolic events and bleeding in cancer patients. However, there is insufficient data regarding the safety and activity of thrombolytic agents in cancer patients receiving bevacizumab-based therapy. In the present case, despite the increased risk of bleeding, low-dose and prolonged tissue plasminogen activator infusion was effectively and reliably applied to treat a massive pulmonary embolism, which resulted in hemodynamic instability in the patient.
    Oncology letters 12/2014; 8(6):2779-2781. · 0.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Arterial ischemia and hemorrhage are associated with bevacizumab, an inhibitor of vascular endothelial growth factor that is widely used to treat many types of cancers. As specific types of arterial ischemia and hemorrhage, cerebrovascular events such as central nervous system (CNS) ischemic events and CNS hemorrhage are serious adverse events. However, increased cerebrovascular events have not been uniformly reported by previous studies. New randomized controlled trials (RCTs) have been reported in recent years and we therefore conducted an up-to-date meta-analysis of RCTs to fully characterize the risk of cerebrovascular events with bevacizumab. We searched the databases of PubMed, Web of Science, and the American Society of Clinical Oncology conferences to identify relevant clinical trials up to February 2014. Eligible studies included prospective RCTs that directly compared patients with cancer treated with and without bevacizumab. A total of 12,917 patients from 17 RCTs were included in our analysis. Patients treated with bevacizumab had a significantly increased risk of cerebrovascular events compared with patients treated with control medication, with a relative risk of 3.28 (95% CI, 1.97-5.48). The risks of CNS ischemic events and CNS hemorrhage were increased compared with control, with RRs of 3.22 (95% CI, 1.71-6.07) and 3.09 (95% CI, 1.36-6.99), respectively. Risk varied with the bevacizumab dose, with RRs of 3.97 (95% CI, 2.15-7.36) and 1.96 (95% CI, 0.76-5.06) at 5 and 2.5 mg/kg/week, respectively. Higher risks were observed in patients with metastatic colorectal cancer (RR, 6.42; 95% CI, 1.76-35.57), and no significant risk was observed in other types of tumors. In conclusion, the addition of bevacizumab significantly increased the risk of cerebrovascular events compared with controls, including CNS ischemic events and CNS hemorrhage. The risk may vary with bevacizumab dose and tumor type.
    PLoS ONE 07/2014; 9(7):e102484. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Compared with the general population, cancer patients have a higher risk of venous thromboembolism as well as arterial thrombotic events such as stroke, myocardial infarction and peripheral arterial embolism. Therefore a possible concern for women with malignancies undergoing ovarian stimulation for fertility preservation is the increased risk of venous or arterial thrombosis.
    Human Reproduction Update 07/2014; · 8.66 Impact Factor