Treatment of advanced colorectal cancer

Colorectal cancer is one of the most chemotherapy-resistant human malignancies. After 30 years of intensive research, 5-fluorouracil (5-FU) remains the most frequently used drug. The expected response rate is of about 15% without any proven benefit in survival. One of the combination most investigated recently has been methyl CCNU, 5-FU, vincristine and streptozotocine (MOF-S). It has shown a response rate of 30-40% but only little benefit in survival. Although cisplatin (CDDP) is inactive as a single agent, the combination of 5-FU and cisplatin (CDDP) might still be of interest when CDDP is fractionated over 3 to 5 days and 5-FU given as a continuous infusion. Local treatment using the intra-arterial and the intraportal route gives rather high response rates, but has not shown any benefit in survival. Biochemical modulation using allopurinol, methotrexate and leucovorin has raised considerable interest, but at the present time no major benefit in survival has been disclosed.