Colorectal cancer: integrating oxaliplatin

5-Fluorouracil (5-FU), used according to several types of administration and several modulations, remained the standard treatment of colorectal cancer for many years. However, two major drugs (irinotecan and oxaliplatin) improved the therapeutic possibilities for this disease. Both drugs are active as a single agent, but they have a clear in vitro and in vivo synergistic antitumoral activity when combined with modulated 5-FU. Significant improvements in response rate, progression-free survival, and overall survival have been obtained by irinotecan/5-FU and oxaliplatin/5-FU combinations compared to 5-FU alone. Integrating these drugs in the therapeutic strategy of metastatic colorectal cancer treatment was a challenge for clinical trials. Second- and third-line treatments are often used, and these treatments are a large reason for the improvement in survival. Each patient who is able to receive several lines of therapy should be offered this strategy. Many attempts to optimize the results of these combinations have been performed. Although no definitive data show one drug to be better than the other, several arguments favored the oxaliplatin/5-FU combination as a first-line treatment of metastatic colorectal cancer. A better collaboration between surgeons and oncologists, based on the improvement of surgical techniques and highly active chemotherapeutic regimens, provides patients more strategies with curative intent in liver and lung metastatic disease. Progress in treating metastatic disease will hopefully translate into the improvement of cure rates when applied to adjuvant therapy. The tolerance of the oxaliplatin/5-FU combination allows for design regimens integrating new drugs, such as biologic modifiers.