Target Practice: Lessons from Phase III Trials with Bevacizumab and Vatalanib in the Treatment of Advanced Colorectal Cancer

Abstract

LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Describe the safety of using bevacizumab in clinical practice.2. Explain the benefit of adding bevacizumab to chemotherapy in colorectal cancer.3. Discuss mechanisms of targeting the VEGF/VEGFR pathway.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME Disclosure of potential conflicts of interest is found at the end of this article. ABSTRACT

Akt-Activated Endothelium Constitutes the Niche for Residual Disease and Resistance to Bevacizumab in Ovarian Cancer

“…Subsequently, the first antiangiogenic molecule developed to impair neoangiogenesis targeted VEGF. Bevacizumab (Avastin, Genentech Inc.) is a humanized monoclonal antibody directed against all isoforms of VEGF-A (8). Bevacizumab prevents the binding of VEGF-A to its receptor VEGF-R1 (Flt-1) and R2 (Flt-2 or KDR).…”

The VEGF Pathway in Cancer and Disease: Responses, Resistance, and the Path Forward

“…Preclinical data for the activity of these (and many other) VEGF pathway inhibitors are beyond the scope of this review (Timar and Dome 2008). Based on promising single agent or combination therapy, many inhibitors have entered human clinical trials for a wide range of diseases and have been thoroughly reviewed (see Table 2) (Kowanetz and Ferrara 2006;Ho and Kuo 2007;Kourlas and Abrams 2007;Los et al 2007). …”

Review: Incidence and clinical significance of Bevacizumab-related non-surgical and surgical serious adverse events in metastatic colorectal cancer

“…(WHC), serious bleeding, arterial and venous thromboembolic events (ATE and VTE), renal toxicity and influences on liver parenchyma 5,[7][8][9][10][11][12][13] . Pharmacokinetic studies show that BV has a half-life of 20 days [range 11-50 days].…”

“…It has 2 potentially cytostatic effects: prevention of neovascularization and normalization of immature and abnormal blood vessels 1,4,5 . This is assumed to retard the shedding of metastatic cells in the circulation and improve the delivery of therapeutic agents in tumors 6 .…”

“…Therefore, one can expect an anti-VEGF agent, such as BV, to cause mechanism-related serious adverse events (SAE) due to the reduction of VEGF availability 5 . The most frequently described side effects are arterial hypertension (AHT), gastrointestinal (GI) perforations, wound healing complications M A N U S C R I P T…”