Pharmacology Xagena

Avastin increases risk of gastrointestinal perforation

Cancer patients treated with Bevacizumab ( Avastin ) in combination with chemotherapy are at significantly greater risk of potentially life-threatening gastrointestinal perforations, particularly patients with advanced colorectal cancer and renal cell cancer.

Bevacizumab belongs to a class of drugs called angiogenesis inhibitors, that slow down the growth of tumours by cutting off their blood supply. Bevacizumab has been shown to be beneficial in the treatment of many types of cancer including colorectal cancer, renal cell cancer, non-small cell lung cancer. Despite concerns about the use of Bevacizumab and gastrointestinal perforation, including a black-box warning issued by the FDA ( Food and Drug Administration ) to discontinue Bevacizumab in patients with gastrointestinal perforation, the link is not well established and so far no trials have proved a significant association.

To resolve this uncertainty, Shenhong Wu and colleagues from Stony Brook University Cancer Center, New York, did a meta-analysis of 17 randomised trials involving 12,294 patients with a variety of solid tumours to assess the role of Bevacizumab in gastrointestinal perforation. The authors also examined whether the dose of Bevacizumab or having a specific type of cancer was related to a higher risk of developing gastrointestinal perforation.

Findings showed that the incidence of gastrointestinal perforation was 0.9%, with a two-fold increased risk of gastrointestinal perforation in patients receiving Bevacizumab compared with controls, and a mortality of 21.7% in patients who developed gastrointestinal perforation. Interestingly, the likelihood of developing gastrointestinal perforation was found to be dose-dependent. Versus controls, lower doses of Bevacizumab ( 2.5 mg/kg per week ) increased risk of gastrointestinal perforation by 61%; while at a higher dose ( 5 mg/kg per week ), the risk of a gastrointestinal perforation increased by 167%.

The incidence of gastrointestinal perforation with Bevacizumab also varied among different tumours, with the highest incidence observed among patients with advanced colorectal cancer and renal cell cancer, and the lowest in patients with pancreatic cancer.

The authors have concluded that as Bevacizumab is extensively used in routine cancer treatment, it will be increasingly important to recognise symptoms indicating perforation and intervene promptly to reduce morbidity and fatality. The study might help to identify a subset of patients receiving Bevacizumab at high risk of Bevacizumab-associated perforation.

Source: Lancet Oncology, 2009