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Bevacizumab
General information
Bevacizumab is an anti-angiogenic agent that has been rationally designed to target vascular endothelial growth factor (VEGF), a key mediator in angiogenesis. It was approved by the FDA in February 2004 for the first-line treatment of metastatic colorectal cancer in combination with 5-fluorouracil-based chemotherapy, and is the first approved agent to target angiogenesis [ ].
The principal adverse events seen in clinical trials are hypertension, proteinuria, arterial thrombosis, effects on wound healing, bleeding, and gastrointestinal perforation. These events are for the most part mild to moderate intense and clinically manageable (hypertension, proteinuria, minor bleeding) or are uncommon (wound healing complications, gastrointestinal perforation, and arterial thrombosis). The adverse effects profile of bevacizumab makes it a suitable adjunct to standard chemotherapy, and it is now approved for use in the USA, the European Union, and other markets worldwide [ ; for the use of bevacizumab in the treatment of choroidal neovascularization see chapter 47]. Hypertension has been associated with bevacizumab [ ]. Close monitoring, especially in patients who are at greater risk of adverse events, is important [ ].
The use of bevacizumab to target blood vessels in the treatment of solid tumors has been reviewed [ ], as have its many adverse effects [ ].
Bevacizumab has similar efficacy to ranibizumab and aflibercept in age-related macular degeneration [ ].
Drug studies
Observational studies
The short-term and long-term safety of topical bevacizumab 5 mg/ml for progressive corneal neovascularization secondary to a variety of corneal diseases and not responding to conventional anti-inflammatory treatment have been evaluated in 30 eyes of 27 patients [ ]. Five patients (five eyes) developed new corneal epithelial defects. The authors warned against using bevacizumab in patients with epithelial defects and neurotrophic keratopathy. There were no allergic reactions, ocular drug-related complaints, or systemic adverse reactions.
Comparative studies
In three comparative trials there was an increase in median survival time of 3.7 months (18.8 versus 15.1 months) when bevacizumab was added to a fluorouracil + folinic acid combination [ ]. When added to current chemotherapy protocols bevacizumab increased the frequency of some potentially serious reactions, such as cardiovascular disorders (hypertension, arterial thrombosis); tumour hemorrhage; intestinal perforation; impaired wound healing; and hematological disorders (such as severe leukopenia).
Drug-combination studies
In a phase II trial, bevacizumab 5 mg/kg (n = 33) or 10 mg/kg (n = 33) was given in combination with fluorouracil + leucovorin to patients with metastatic colorectal cancer [ ]. Fluorouracil + leucovorin (n = 36) without bevacizumab served as the control arm. The most common adverse effects were diarrhea, leukopenia, and stomatitis attributable to fluorouracil + leucovorin. Bevacizumab was associated with a higher incidence of headache, rash, chills, epistaxis, and hypertension. Two patients had gastrointestinal bleeding with bevacizumab 5 mg/kg and five with 10 mg/kg. Thrombotic complications occurred in 9% in the control arm, 26% with bevacizumab 5 mg/kg, and 13% with bevacizumab 10 mg/kg.
Organs and systems
Cardiovascular
Bevacizumab 5 mg/kg intravenously every 2 weeks can cause mild hypertension [ ].
In a systematic review of 11 placebo-controlled trials in 8341 patients of ranibizumab, bevacizumab, and aflibercept, systemic thrombotic events occurred more often with all three drugs than with placebo [ ].
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