New therapies, new directions: advances in the systemic treatment of metastatic colorectal cancer.

Colorectal cancer is the second leading cause of cancer death and it is clear that patients with metastatic disease have better quality of life and survival when given treatment. Despite four decades of experience of treating patients with fluorouracil, there remains considerable controversy about the optimum dose and scheduling, as well as biomodulation with leucovorin and methotrexate. However, irrespective of the dose and schedule, overall survival times are poor--about 1 year. Disappointingly, oral agents with similar mechanisms to fluorouracil do not improve survival rates in comparison with fluorouracil and leucovorin treatment. Irinotecan and oxaliplatin are newer agents that have improved the response rates for patients with metastatic disease when they are added to flurouracil and leucovorin. The combination of irinotecan, fluorouracil, and leucovorin has also improved overall survival. These are small advances in the fight against colorectal cancer, and further drug development is necessary.