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Bert H. O’Neil, MD

Articles by Bert H. O’Neil, MD

Worldwide, hepatocellular carcinoma is the fifth most common malignancy and the third most common cause of cancer mortality. Most patients with hepatocellular carcinoma suffer from cirrhosis primarily caused by alcoholism or chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV); decades may pass between infection with viral hepatitis and development of this cancer. The approximately equal annual incidence and mortality of 1 million reported around the world stands as evidence of its lethality.

The use of engineered monoclonal antibodies as antineoplastic therapy has been a significant advance within the past 15 years. These agents target various receptors and ligands required for the proliferation, survival, or maintenance of angiogenesis of tumors. Currently there are several agents approved by the US Food and Drug Administration for clinical use in solid tumors. Bevacizumab (Avastin) is a humanized monoclonal antibody that targets the vascular endothelial growth factor (VEGF) and inhibits angiogenesis, and is currently approved for the treatment of colorectal, lung, and breast cancer (Avastin package insert, 2008). Trastuzumab (Herceptin) inhibits the HER2/neu receptor, and is utilized in both the adjuvant and palliative settings in breast cancer (Herceptin package insert, 2008).

Because of recent advances ineach discipline we commonlyrecommend and deliver threemodalities-chemotherapy, radiation,and surgery-in the management oflocalized gastrointestinal cancers inpatients who are judged to be suitablecandidates for aggressive therapy.After years of experimentation andsome therapeutic misadventures, combinationchemotherapy can now bedelivered with greater safety and effectiveness.This is based in part onbetter antiemetics, better supportivetherapies such as judicious use of granulocytecolony-stimulating factors,and more accurate models for adjustingdosages based on pharmacokineticand pharmacodynamic profiling.