6 oktober 2011: zie ook nieuwe berichtgeving over risico's van Avastin - bevacizumab in linkerkolom,

26 februari 2011: Ook Medscape maakt nu melding van deze studie en waarschuwt met name vrouwen met borstkanker voor de risico's van Avastin in combinatie met chemo Onderaan heb ik het artikel zoals Medscape dat heeft gepubliceerd gekopieerd.

2 februari 2011: Bron JAMA

Kankerpatiënten met verschillende vormen van kanker lopen een sterk vergroot risico op behandelings gerelateerde fatale bijwerkingen - overlijden, wanneer zij naast hun chemo ook Avastin - Bevacizumab gebruiken. Dit blijkt uit een grote meta analsye van 16 gerandomiseerde studies met meer dan 10.000 kankerpatiënten. We hebben afgelopen jaren vele studies gepubliceerd, zie hiernaast in linkerkolom,  waarin gewaarschuwd werd voor de risico's van het gebruik van Avastin - Bevacizumab en deze studie bevestigt wederom het gevaarlijke van Avastin gebruik. Hier het abstract van de studie:

Treatment-Related Mortality With Bevacizumab in Cancer Patients

A Meta-analysis

  1. Vishal Ranpura, MD;
  2. Sanjaykumar Hapani, MD;
  3. Shenhong Wu, MD, PhD

[+] Author Affiliations

  1. Author Affiliations: Department of Medicine (Dr Ranpura), Division of Hematology and Medical Oncology (Drs Hapani and Wu), Stony Brook University Medical Center, Stony Brook, New York.


Context Fatal adverse events (FAEs) have been reported in cancer patients treated with the widely used angiogenesis inhibitor bevacizumab in combination with chemotherapy. Currently, the role of bevacizumab in treatment-related mortality is not clear.

Objective To perform a systematic review and meta-analysis of published randomized controlled trials (RCTs) to determine the overall risk of FAEs associated with bevacizumab.

Data Sources PubMed, EMBASE, and Web of Science databases as well as abstracts presented at American Society of Clinical Oncology conferences from January 1966 to October 2010 were searched to identify relevant studies.

Study Selection and Data Extraction Eligible studies included prospective RCTs in which bevacizumab in combination with chemotherapy or biological therapy was compared with chemotherapy or biological therapy alone. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated using fixed- or random-effects models.

Data Synthesis A total of 10 217 patients with a variety of advanced solid tumors from 16 RCTs were included in the analysis. The overall incidence of FAEs with bevacizumab was 2.5% (95% CI, 1.7%-3.9%). Compared with chemotherapy alone, the addition of bevacizumab was associated with an increased risk of FAEs, with an RR of 1.46 (95% CI, 1.09-1.94; P = .01; incidence, 2.5% vs 1.7%). This association varied significantly with chemotherapeutic agents (P = .045) but not with tumor types (P = .13) or bevacizumab doses (P = .16). Bevacizumab was associated with an increased risk of FAEs in patients receiving taxanes or platinum agents (RR, 3.49; 95% CI, 1.82-6.66; incidence, 3.3% vs 1.0%) but was not associated with increased risk of FAEs when used in conjunction with other agents (RR, 0.85; 95% CI, 0.25-2.88; incidence, 0.8% vs 0.9%). The most common causes of FAEs were hemorrhage (23.5%), neutropenia (12.2%), and gastrointestinal tract perforation (7.1%).

Conclusion In a meta-analysis of RCTs, bevacizumab in combination with chemotherapy or biological therapy, compared with chemotherapy alone, was associated with increased treatment-related mortality.

Fatal Adverse Events With Bevacizumab

Ranpura V, Hapani S, Wu S
JAMA. 2011;305:487-494

Study Summary

Although bevacizumab has been shown to improve survival in patients with a variety of solid tumors when added to conventional chemotherapy, it has also been associated with life-threatening and fatal adverse events (FAEs), including bleeding, thromboembolism, and perforation. This improvement in survival has led to the assumption that FAEs are rare and do not significantly affect patients who are receiving treatment. In this large meta-analysis, Ranpura and colleagues identified 10,217 patients with various solid tumors from 16 randomized studies, as follows:

  • Colorectal cancer (5 studies);
  • Non-small cell lung cancer (4 studies);
  • Breast cancer (3 studies);
  • Renal cell cancer (2 studies);
  • Pancreatic cancer (1 study); and
  • Prostate cancer (1 study).

A clear increase in FAEs was evident in patients who received bevacizumab compared with those who received standard chemotherapy alone (2.5% vs 1.7%; relative risk 1.46; P = .01). This association varied with chemotherapy agents but not with tumor type. In particular, FAEs occurred in patients receiving taxanes or platinum agents (RR 3.49; 3.3% vs 1%) but not with other specific agents. Types of FAEs included bleeding (23.5%), gastrointestinal perforation (7.1%), and pulmonary embolism and stroke (5.1% each). Most fatal bleeding events were pulmonary or gastrointestinal in origin.


The benefit of bevacizumab is under increased scrutiny given the latest data in patients with metastatic breast cancer. In this large meta-analysis, Ranpura and colleagues documented a clear increase in the rate of FAEs (2.5%) in patients receiving bevacizumab and identified taxane-/platinum-based regimens as being largely responsible for this increase. Of note, patients enrolled in clinical trials typically have fewer comorbidities than patients not enrolled in trials; in bevacizumab studies specifically, patients with recent history of stroke or myocardial infarction were excluded. Therefore, risks for FAEs may be greater in the real-world setting than reported here. The bottom line is: Exercise caution when selecting patients for treatment with bevacizumab, keeping in mind both improvement in survival and risk for FAEs.

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