Chemotherapy: which drug and when?

The treatment of advanced colorectal cancer has become very complex due to: (i) the relative efficacy of therapy, which has turned a rapidly fatal cancer into a more indolent disease in the last 10 years; (ii) the availability of four active chemotherapeutic agents and three biologics; (iii) the efficacy of several lines of therapy; (iv) the rare, but real, chance of curing stage IV patients through the combined use of chemotherapy and surgery. This article will concentrate on chemotherapy (leaving out the biologics) and will review the determinants of how aggressive the initial approach should be, the key factors of our initial treatment choices, when an intense treatment is better than just waiting or using single-agent chemotherapy; which chemotherapy is best for first, second and subsequent lines of treatment.