The importance of vascular endothelial growth factor (VEGF) as a regulator of normal and tumor blood vessel growth has been increasingly characterized over the past two decades. VEGF increases vascular permeability and has a well established role in stimulating angiogenesis, a prerequisite of tumor growth. Numerous compounds have been developed to counteract the angiogenic effects of VEGF. One such drug, bevacizumab, a humanized anti-VEGF monoclonal antibody, received FDA approval in the US earlier this year. Results obtained from initial trials showed that this drug was generally well tolerated, and combination studies of bevacizumab and chemotherapeutic agents have been completed in patients with breast, prostate, lung, and colorectal cancers. A randomized trial of bevacizumab used in combination with capecitabine for metastatic breast patients showed no overall improvement of progression-free survival. However, this result contrasted greatly with the data obtained for patients with advanced colorectal cancer, where a combination regimen of bevacizumab, 5-fluorouracil, leucovorin and irinotecan demonstrated a significant improvement in response rates and overall survival compared with chemotherapy alone. This review highlights the key clinical trial data with bevacizumab and discusses the reasons for some of the contrasting results seen in different patient studies.
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Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285: 1182–1186
Ferrara N (2002) VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer 2: 795–803
Ferrara N et al. (2003) The biology of VEGF and its receptors. Nat Med 9: 669–676
Ferrara N et al. (2004) Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 3: 391–400
Gordon MS et al. (2001) Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol 19: 843–850
Salgaller ML (2003) Technology evaluation: bevacizumab, Genentech/Roche. Curr Opin Mol Ther 5: 657–670
Kerr DJ and La Thangue N. Multitargeted kinase inhibitors: novel trial design. Annals of Oncology, in press
Rugo HS (2004) Bevacizumab in the treatment of breast cancer: rationale and current data. Oncologist 9 (Suppl 1): 43–49
Kindler L et al. (2003) Bevacizumab (B) plus gemcitabine (G) in patients (pts) with advanced pancreatic cancer. Proc Am Soc Clin Oncol 22: 259
DeVore R et al. (2000) A randomized phase III trial comparing rhumab VEGF (recombinant humanised monoclonal antibody to VEGF) plus carboplatin/paclitaxel (CP) to CP alone in patients with stage IIIb/IV non small cell lung cancer. Proc Am Soc Clin Oncol A1896
Carson WE et al. (2003) A phase II trial of recombinant humanized monoclonal anti-vascular endothelial growth factor (VEGF) antibody in patients with malignant melanoma. Proc Am Soc Clin Oncol A705
Willett CG et al. (2004) Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 10: 145–147
Miller KD et al. (2002) Phase III trial of capecitabine (Xeloda) plus bevacizumab (Avastin) versus capecitabine alone in women with metastatic breast cancer (MBC) previously treated with an anthracycline and a taxane. Breast Cancer Res Treat 76: S37
Yang JC et al. (2003) A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349: 427–434
Kabbinavar F et al. (2003) Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 21: 60–65
Hurwitz H et al. (2004) A phase III randomized trial to evaluate the safety and efficacy of adding bevacizumab (rhuMAb VEGF) to bolus IFL in first line metastatic colorectal cancer. N Engl J Med 350: 2335–2342
The author declared that he has received an educational grant from Roche for an adjuvant trial in stage III colorectal cancer patients. Bevacizumab is used in one study group in the trial, and is co-marketed by Roche.
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Kerr, D. Targeting angiogenesis in cancer: clinical development of bevacizumab. Nat Rev Clin Oncol 1, 39–43 (2004). https://doi.org/10.1038/ncponc0026
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