• J L Grem.
• Developmental Therapeutics Department, Medicine Branch, National Cancer Institute, National Naval Medical Center, Bethesda, MD 20889-5105, USA.
• Semin. Oncol. 1997 Oct 1; 24 (5 Suppl 18): S18-8-S18-18.

AbstractA variety of 5-fluorouracil (5-FU)- based chemotherapy regimens have been investigated in colorectal cancer patients in randomized trials over the past decade. The standard regimen for treatment of colorectal cancer is combination 5-FU plus leucovorin (LV). The results from 12 randomized trials indicate that 5-FU/LV is more active than single-agent 5-FU (25% v 14% of evaluable patients); however, median survival was unchanged (12.2 months v 11.4 months, respectively). Furthermore, the weekly and monthly schedules of 5-FU/LV are therapeutically equivalent, although the spectrum of toxicity differs. On the monthly schedule, a LV dose of 200 mg/m2 appears to have no advantage over 20 mg/m2; however, on the weekly schedule, high-dose LV appeared to be slightly more effective than low-dose LV (2-hour infusion) (25% v 18%) at the cost of a higher incidence of severe diarrhea (26% v 14%). Furthermore, similar response rates are observed with the racemic commercial formulation of LV and the pure (I-LV) active stereoisomer. Other modulatory strategies that appear to produce higher response rates than single-agent intravenous push 5-FU include sequential methotrexate/5-FU (19% v 10%) and continuous infusion schedules (22% v 14%). Although 5-FU-modulated strategies improve response rates over those observed with single-agent 5-FU, median survival in multi-institutional trials unfortunately has not generally exceeded 12 months. The mechanism of action, clinical activity, and toxicity of single-agent 5-FU and 5-FU-modulated regimens are reviewed.

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