Systemic treatment options in advanced colorectal cancer: perspectives on combination 5-fluorouracil plus leucovorin.
A 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.
Grem
J L
JL
Developmental Therapeutics Department, Medicine Branch, National Cancer Institute, National Naval Medical Center, Bethesda, MD 20889-5105, USA.
D000931:Antidotes / Q000008:administration & dosage / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D002955:Leucovorin / Q000008:administration & dosage / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
D000931:Antidotes; D000964:Antimetabolites, Antineoplastic; D007155:Immunologic Factors; D002955:Leucovorin; D005472:Fluorouracil