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Medline ® Abstract for Reference 84

of 'Toxicity of molecularly targeted antiangiogenic agents: Non-cardiovascular effects'

Gastrointestinal perforation associated with bevacizumab use in metastatic colorectal cancer: results from a large treatment observational cohort study.
Kabbinavar FF, Flynn PJ, Kozloff M, Ashby MA, Sing A, Barr CE, Grothey A
Eur J Cancer. 2012 May;48(8):1126-32. Epub 2012 Mar 15.
BACKGROUND: Bevacizumab prolongs overall and progression-free survival when added to fluorouracil-based chemotherapy in patients with metastatic colorectal cancer in randomised controlled trials (RCTs). However, gastrointestinal perforation (GIP) occurs in 1-2% of treated patients. We sought to describe the incidence, temporal pattern, outcomes and potential risk factors for GIP in a large, community-based observational cohort study of patients treated with bevacizumab.
PATIENTS AND METHODS: Baseline patient and tumour characteristics, including potential GIP risk factors, were collected at study entry. Treatment, targeted adverse events, progression events and survival data were recorded every 3 months. Detailed clinical information was collected for all patients experiencing a GIP event. Effects of baseline risk factors on GIP risk were investigated using Cox proportional hazards regression.
RESULTS: Of 1953 evaluable patients followed for a median of 20.1 months,37 (1.9%) experienced GIP. Most GIP events were surgically managed with successful outcomes; four events were fatal. The majority of GIP events (26/37) occurred≤6 months after starting bevacizumab (median, 3.35 months). Univariate and multivariate analyses showed that age≥65 years was significantly associated with lower GIP risk. In multivariate analyses, intact primary tumour and prior adjuvant radiotherapy were significantly associated with increased risk of GIP within 6 months after starting bevacizumab. A regression analysis that assessed the risk of GIP over time showed no cumulative risk associated with bevacizumab exposure.
CONCLUSION: The observed rate of GIP in this large, community-based experience was consistent with rates reported in RCTs. Most events were successfully managed with surgical intervention.
Department of Medicine, Division of Hematology&Oncology, University of California at Los Angeles, 924 Westwood Blvd, Los Angeles, CA 90095-7207, USA.