Bevacizumab: new drug. Metastatic colorectal cancer: good in theory, not in practice.

(1) The prognosis for metastatic colorectal cancer is grim. The best treatment results are obtained by adding irinotecan to first-line fluorouracil + folinic acid therapy and then oxaliplatin to second-line fluorouracil + folinic acid therapy (or the reverse sequence), but median survival time still fails to exceed 2 years. (2) Bevacizumab is a monoclonal antibody directed against vascular endothelial growth factor (VEGF), a mediator involved in angiogenesis. Bevacizumab is marketed in Europe for first-line treatment of metastatic colorectal cancer, in combination with fluorouracil + folinic acid (with or without irinotecan). (3) The clinical evaluation includes 3 comparative trials. A double-blind trial involving 813 patients compared the American IFL protocol (irinotecan + fluorouracil + folinic acid) + placebo with the IFL protocol + bevacizumab. Median survival time was shorter with IFL + placebo (15.6 versus 20.3 months), but the results are difficult to extrapolate to the situation in Europe, where the FOLFIRI protocol is used (irinotecan + fluorouracil + folinic acid). This protocol is more effective than the IFL protocol. (4) Another double-blind trial, involving 204 patients, compared another American protocol, fluorouracil + folinic acid + placebo, with fluorouracil + folinic acid + bevacizumab. Median survival time did not differ significantly between the groups (12.9 and 16.6 months). (5) A combined analysis of 3 comparative trials showed an increase in median survival time of 3.3 months (17.9 versus 14.6 months) when bevacizumab was added to a fluorouracil + folinic acid combination. An indirect comparison suggests that this is no better than adding irinotecan. (6) In second-line treatment, preliminary data from a trial of bevacizumab + FOLFOX 4 (oxaliplatin + fluorouracil + folinic acid) fail to show a tangible benefit for bevacizumab. (7) Bevacizumab adjunction to current chemotherapy protocols increased the frequency of some potentially serious reactions, such as cardiovascular disorders (hypertension, arterial thrombosis); tumour haemorrhage; intestinal perforation; wound healing; and haematological disorders (severe leukopenia, etc.). (8) In practice, there is no evidence that bevacizumab is any better than current European chemotherapy protocols for first-line treatment of metastatic colorectal cancer.