[Anti-angiogenic treatment and colorectal cancer].
For many years, oncology research has focused on the study of therapeutic agents able to target a different cell than a cancer cell. Tumor angiogenesis mediated by the vascular endothelial growth factor (VEGF) was one of the pathways investigated. The treatment of metastastic colorectal cancer has dramatically evolved. Overall survival has significantly improved, owing to the use in standard daily practice of irinotecan and oxaliplatin, combined with 5-fluorouracil (5FU) and leucovorin. This review summarizes efficacy and safety data of two antiangiogenic agents, bevacizumab (a monoclonal antibody inhibiting VEGF) and vatalanib (a tyrosine kinase inhibitor of VEGF), assessed in phase III trials in metastastic colorectal cancer. The efficacy of bevacizumab combined with 5FU-leucovorin +/- irinotecan based on overall survival data which was demonstrated in the first-line treatment of metastastic colorectal cancer in studies conducted in the US, has recently been demonstrated in the same indication based on progression survival when combined to oxaliplatin and a fluoropyrimidine (capecitabine or 5FU-leucovorin). Bevacizumab combined to infusion chemotherapy with 5FU-leucovorin with or without irinotecan is indicated, in Europe, in the first-line treatment of metastastic colorectal cancer. While in the US, prescription options are wider in the first-line treatment, it is combined to chemotherapies with a fluoropyrimidine +/- irinotecan or oxaliplatin, and in second line as well with fluoropyrimidine and oxaliplatin. Several questions regarding the optimal use of bevacizumab still remain to be answered in the treatment of metastastic colorectal cancer. Vatalanib has not shown benefit in this pathology.
André
Thierry
T
Service d'oncologie médicale, hôpital Tenon, 4, rue de la Chine, 75970 Paris Cedex 20. thierry.andre@tnn.aphp.fr
Tournigand
Christophe
C
Abbas
Fadi
F
Louvet
Christophe
C
de Gramont
Aimery
A
D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000188:drug therapy; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007416:Intestinal Perforation / Q000139:chemically induced; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010793:Phthalazines / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D013923:Thromboembolism / Q000139:chemically induced; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D014945:Wound Healing / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D010793:Phthalazines; D011725:Pyridines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; C404768:vatalanib