Bevacizumab in the Treatment of Metastatic Colorectal Cancer: Safety Profile and Management of Adverse Events

Bevacizumab is well suited for use in combination with first- or second-line chemotherapy in the treatment of metastatic colorectal cancer because its side effects are predictable and appear not to add to the incidence or severity of the side effects of chemotherapy. Clinical trials of bevacizumab in combination with oxaliplatin-containing and 5-fluorouracil-based regimens have shown that combination therapy is well tolerated and its toxicity is not substantially greater than that of the chemotherapy alone. Preliminary data from community-based and observational studies show that the incidence and severity of adverse events with combinations of bevacizumab and newer chemotherapy regimens are similar to those in the pivotal phase III trial with irinotecan, 5-fluorouracil, and leucovorin plus bevacizumab. Across trials, these side effects include a greater risk of grade 3 hypertension and grade 1 or 2 proteinuria, a slight increase (<2 percentage points) in grade 3 or 4 bleeding, and impaired surgical wound healing in patients who undergo surgery during treatment with bevacizumab. Potentially life-threatening events (arterial thrombotic events and gastrointestinal perforation) have occurred in a small number of patients. Close patient monitoring, especially in patients who are at greater risk of adverse events, is important.