Overview of bevacizumab: a new cancer therapeutic strategy targeting vascular endothelial growth factor.
OBJECTIVE
The pharmacology, pharmacokinetics, preclinical and clinical experience to date, and clinical concerns in monitoring patients receiving bevacizumab, recombinant humanized monoclonal antibody to vascular endothelial growth factor (VEGF), are described.


CONCLUSIONS
Preclinical research revealed that bevacizumab specifically inhibits VEGF, has activity in multiple cancer cell lines, and is synergistic with several cancer chemotherapeutic agents. In humans, bevacizumab has a long half-life, allowing intravenous administration once every two to three weeks. Dose-limiting toxicities, the formation of antibodies to bevacizumab, and problems with wound healing after surgery have not been observed in clinical trials. A phase II study of bevacizumab in combination with 5-fluorouracil and leucovorin in patients with metastatic colorectal cancer showed promising results (i.e., therapeutic response rate and disease-free progression of survival), although a clear dose-response relationship was not demonstrated and concerns were raised about the potential for thromboembolic events, bleeding, hypertension, and proteinuria. In a phase III study in patients with refractory metastatic breast cancer, bevacizumab doubled the response rate from capecitabine but it did not affect survival. First-line use of bevacizumab with irinotecan, orouracil, and leucovorin produced significant improvements in response rate, duration of response, and survival in a phase III study of patients with metastatic colorectal cancer. Bevacizumab was associated with hypertension, which was readily managed with mild antihypertensive agents, and possibly with gastrointestinal (GI) perforation, but not with serious bleeding, thromboembolism, or proteinuria. Nevertheless, patients receiving bevacizumab should be monitored for GI perforation, bleeding, thromboembolism, hypertension, and proteinuria, especially if they have a condition that predisposes them to these problems (e.g., a history of unusual bleeding or clotting, hypertension, or proteinuria; use of anticoagulants or other medications that affect clotting or coagulation).


CONCLUSIONS
In clinical trials, bevacizumab has shown promise in promoting synergism with other chemotherapeutic agents in the treatment of various cancers.
Ignoffo
Robert J
RJ
University of California-San Francisco, 1327 Grand Avenue, San Rafael, CA 94901-2232, USA. bobi@itsa.ucsf.edu
D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab