Targeted agents to improve treatment results in colon cancer: bevacizumab and cetuximab.
The addition of bevacizumab (BEV) and cetuximab to chemotherapy in the treatment of metastatic colorectal cancer (MCRC) has resulted in an increase of progression-free survival (PFS) and overall survival. BEV is usually given in the first line setting and can be combined with any chemotherapeutic regimen. BEV has activity also in the second line setting but not in the third line. It has been proven to be safe in the community setting (BRiTE) and in the post-marketing study (BEAT), and confirmed its efficacy and safety in the first line with all regimens of chemotherapy. In addition, retrospective analyses demonstrate that surgery with curative intent can be performed in about 20% of the patients on BEV. Cetuximab has activity and prolongs survival in third line and above setting as observed in the NCIC study and PFS in the BOND study in patients failing irinotecan-based chemotherapy. Cetuximab increases PFS in the second line setting, as seen in the EPIC study. In the first line setting (CRYSTAL study), cetuximab increased PFS. Moreover, the percentage of patients undergoing curative resection for colorectal cancer is tripled. Skin toxicity is related to survival. In patients not having skin toxicity, dose escalation (EVEREST study) increased skin toxicity and response rate. Combination of biologicals is feasible (BOND- 2), but financial considerations constitute a problem. BEV is approved for first and second line treatments, and cetuximab is approved in patients failing irinotecan.
Klein
Baruch
B
Institute of Oncology, Meir Medical Center, Kfar Saba, Israel. Baruch.Klein@clalit.org.il
Gottfried
Maya
M
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D000068258:Bevacizumab; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000191:economics / Q000378:metabolism / Q000401:mortality; D018572:Disease-Free Survival; D016527:Drug Costs; D006801:Humans; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000517:prevention & control*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012871:Skin Diseases / Q000139:chemically induced; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000068818:Cetuximab; D018719:Erb-b2 Receptor Tyrosine Kinases; D042461:Vascular Endothelial Growth Factor A; C467484:VEGFA protein, human; C508053:ERBB2 protein, human