Bevacizumab in the treatment of metastatic colorectal cancer (mCRC) in second- and third-line settings.

There are several treatment options for patients with metastatic colorectal cancer (mCRC), including those with disease that has progressed after treatment with chemotherapy. Bevacizumab-containing regimens show good efficacy in patients with previously treated disease. Compared with infused 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX-4), overall survival and progression-free survival are significantly longer with FOLFOX-4 in combination with bevacizumab as second-line treatment in patients with advanced or mCRC. In addition, the response rates and time to progression are greater with the combination of bevacizumab, cetuximab, and irinotecan in patients with irinotecan-refractory mCRC compared with cetuximab and irinotecan therapy. This combination is well tolerated, with no additive toxicities reported. The role of bevacizumab in the treatment of patients with disease refractory to 5-fluorouracil, irinotecan, and oxaliplatin is less clear, owing to inconclusive results in a multicenter study in this population. More research is necessary to determine the efficacy of combinations with bevacizumab in the third- and later-line settings. However, bevacizumab clearly provides significant clinical benefits in previously treated patients with mCRC. On the basis of these benefits and in addition to its approval in the first-line setting, bevacizumab in combination with intravenous 5-fluorouracil-based chemotherapy recently received US Food and Drug Administration approval for the second-line treatment of patients with mCRC.