ABSTRACT
During the past few decades, the overall prognosis of colorectal cancer has not essentially changed. It remains one of the major causes of cancer death in developed countries, and about 40-50% of patients will die of their disease, predominantly due to metastatic spread. Until the late 1980s, therapeutic options for patients with advanced colorectal cancer were almost exclusively based on fluoropyrimidines. Single-agent 5-fluorouracil (5-FU) predominantly administered as intravenous bolus injection was the standard of care for more than 30 years until it was replaced in the early 1990s by the combination of 5-FU plus folinic acid (FA, leucovorin), which demonstrated a greater antineoplastic activity than 5-FU alone.1 With bolus 5-FU/FA administered either five times daily every 4 weeks (the Mayo regimen; see Chapter 41) or once-weekly 6 (the Roswell Park regimen; see Chapter 42), an overall response rate of about 20% and median survival times of 12 months were achieved.1 Further improvements in the systemic treatment of colorectal cancer occurred with the introduction of infusional 5FU/FA regimens administered once-weekly as a 24or 48-hour infusion or on a biweekly 48-hour infusional schedule. Compared with bolus 5-FU/FA, infusional 5-FU/FA induced higher response rates (30-40%), longer progression-free intervals/times to progression (6-7 months), and median survival times of up to 17 months.2,3 In the past decade, a number of new compounds have been developed and introduced into the clinic that demonstrated activity in colorectal cancer; these include oxaliplatin, raltitrexed, oral 5-FU-prodrugs (capecitabine, UFT, and S1), and irinotecan.
