Bevacizumab: An angiogenesis inhibitor with efficacy in colorectal and other malignancies

OBJECTIVE: To review the pharmacology, pharmacokinetics, and pivotal clinical trials for bevacizumab, emphasizing its use in colorectal cancer. DATA SOURCES: A PubMed/MEDLINE search was conducted (1966-April 2004) using the following terms: bevacizumab, Avastin, anti-VEGF, anti-angiogenesis, and colorectal cancer. Additional data sources included meeting abstracts, bibliographies from identified articles, and information from the manufacturer. STUDY SELECTION AND DATA EXTRACTION: Preclinical and clinical trials that used bevacizumab for the treatment of colorectal cancer and other malignancies were selected from the data sources. All published, randomized clinical trials evaluating bevacizumab in colorectal cancer were included in this review. DATA SYNTHESIS: Despite advances in chemotherapy, current therapeutic options for metastatic disease provide only temporary benefit for most patients. Bevacizumab is the first anti-cancer agent shown to provide benefit for patients with cancer by inhibiting angiogenesis. Bevacizumab has shown significant activity in the treatment of many cancers, including metastatic colorectal cancer. When used in combination with fluorouracil-based chemotherapy, bevacizumab improves overall response rates, time to progression, and survival in patients with metastatic colorectal cancer. Common toxicities associated with bevacizumab include hypertension, bleeding episodes, and thrombotic events. CONCLUSIONS: Although clinical knowledge on the effectiveness of bevacizumab is limited, early data indicate that it is a promising agent, with a novel mechanism of action, for patients with metastatic cancer, including colorectal cancer.