Two Steps Forward in the Treatment of Colorectal Cancer

English Version

Until recently, fluorouracil was the only effective systemic treatment for colorectal cancer. It acts primarily by inhibiting thymidylate synthase, a key enzyme in DNA synthesis, and because leucovorin (folinic acid) enhances this effect, fluorouracil and leucovorin (FL) are given together. FL has been given in various dose schedules, with a continuous in fusion appearing slightly more effective than a bolus. FL reduces tumor size by 50 percent or more (objective response) in approximately 20 percent of patients with advanced colorectal cancer and prolongs median survival from approximately 6 months (without treatment) to about 11 months. When given as adjuvant therapy after the complete resection of a colon cancer that has spread to regional lymph nodes (stage III disease), FL increases the probability of remaining free of tumor (diseasefree survival) at five years from approximately 42 percent to 58 percent and the likelihood of surviving for five years (overall five-year survival) from about 51 percent to 64 percent. The use of adjuvant FL in patients without involvement of regional lymph nodes (stage II disease) is controversial; for them, the probability of five-year disease-free survival increases from 72 percent to 76 percent after treatment, but the likelihood of overall survival is approximately 80 percent for treated and untreated patients alike.

During the past five years, the Food and Drug Administration (FDA) has approved four new treatments for advanced colorectal cancer. Two of them (irinotecan [Camptosar] and oxaliplatin [Eloxatin]) are traditional cytotoxic drugs, whereas the other two (cetuximab [Erbitux] and bevacizumab [Avastin]) are monoclonal antibodies against molecular targets.

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