Where do we stand with 5-fluorouracil?

Semin Oncol. 1999 Dec;26(6):589-605.


For nearly four decades, 5-fluorouracil (5-FU) has been the mainstay of treatment for colorectal cancer. Due to the lack of other agents with significant activity, tremendous efforts have been undertaken to increase the efficacy of 5-FU by investigating alternative schedules of delivery and biomodulation. However, bolus 5-FU in combination with folinic acid (FA), either as the Mayo Clinic or Roswell Park protocol, still represents the standard treatment for adjuvant and first-line palliative chemotherapy of colorectal cancer. In a recent meta-analysis, infusional protocols of 5-FU demonstrated increased response rates (14% to 22%) and a marginal, but significant survival benefit of 3 weeks (11.3 to 12.1 months). In view of the much higher costs and complicated management of infusional 5-FU regimens, this marginal survival benefit does not yet allow protracted 5-FU application to be defined as standard therapy. However, protracted 5-FU infusion in combination with radiation can be considered standard therapy as adjuvant treatment of rectal cancer, since it has demonstrated a significant increase in survival. In the future, oral 5-FU prodrugs may be substituted for infusional 5-FU. Furthermore, current data indicate that 5-FU will also be an essential component of combination chemotherapy protocols with the new active agents oxaliplatin, irinotecan, and raltitrexed. Preclinical studies show synergistic antitumor activity of 5-FU with these agents, which corresponds well with clinical response rates of 50% in untreated and 15% to 25% in 5-FU-refractory patients. Moreover, 5-FU-based pro-drug-active drug systems serve as excellent models for tumor-targeted gene therapy.

Publication types

  • Review

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacokinetics
  • Antimetabolites, Antineoplastic / pharmacology
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Aspartic Acid / administration & dosage
  • Aspartic Acid / analogs & derivatives
  • Chronotherapy
  • Colorectal Neoplasms / drug therapy*
  • Dipyridamole / administration & dosage
  • Drug Synergism
  • Fluorouracil / administration & dosage
  • Fluorouracil / pharmacokinetics
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use*
  • Humans
  • Interferons / administration & dosage
  • Leucovorin / administration & dosage
  • Levamisole / administration & dosage
  • Methotrexate / administration & dosage
  • Phosphonoacetic Acid / administration & dosage
  • Phosphonoacetic Acid / analogs & derivatives
  • Radiation-Sensitizing Agents / therapeutic use
  • Trimetrexate / administration & dosage
  • Zidovudine / administration & dosage


  • Antimetabolites, Antineoplastic
  • Radiation-Sensitizing Agents
  • Levamisole
  • Aspartic Acid
  • Zidovudine
  • Dipyridamole
  • sparfosic acid
  • Interferons
  • Phosphonoacetic Acid
  • Leucovorin
  • Fluorouracil
  • Trimetrexate
  • Methotrexate