Second-line therapy for advanced colorectal cancer.

The availability of irinotecan and oxaliplatin has dramatically altered both first- and second-line treatment of advanced colorectal cancer (CRC) compared with the era in which the sole treatment option in advanced disease was 5-fluorouracil (5-FU). Treatment options and strategies are becoming ever more enriched and complex with the recent availability of biologic agents such as bevacizumab and cetuximab. This article reviews randomized clinical trials assessing second-line treatment after failure of first-line single-agent 5-FU, irinotecan-based treatment, or oxaliplatin-based treatment. A number of conclusions can be drawn based on available data. (1) Second-line chemotherapy with active agents is superior to best supportive care alone. (2) Following 5-FU failure, active regimens include irinotecan, FOLFIRI, FOLFOX, and IROX, with IROX appearing to be superior to FOLFIRI. (3) Following irinotecanbased first-line treatment, FOLFOX is in general the best choice, and the combination of FOLFOX plus bevacizumab appears to be superior to FOLFOX alone. (4) Following first-line FOLFOX, irinotecan and FOLFIRI are currently the most appropriate options. Irinotecan plus cetuximab should emerge as an effective regimen. Further study is needed to define the best options in second-line therapy following the FOLFOXIRI triplet or the combination of bevacizumab plus chemotherapy. Studies are ongoing to determine optimal use of biologic agents, both in terms of when they should be used and in what combinations.