Fluorouracil in colorectal cancer--a tale of two drugs: implications for biochemical modulation.
OBJECTIVE
To determine if fluorouracil (FUra) has different mechanisms of action as a function of the dose schedule used.


METHODS
The preclinical and clinical literature relating toxicity and antitumor effects of FUra as a function of its dose schedule, with and without modulating agents, was reviewed.


RESULTS
The data support the hypothesis that FUra may be considered to be two different drugs, depending on its dose schedule (bolus v continuous infusion [CI]).


CONCLUSIONS
These results suggest that additional therapeutic benefit may be obtained from FUra regimens by (1) appropriate schedule-dependent modulation, (2) the sequential or alternating use of cycles of bolus followed by cycles of CI FUra appropriately modulated, or (3) hybrid regimens, ie, those that contain both pulse and CI schedules.
Sobrero
A F
AF
Chair of Medical Oncology, University of Florence, Italy.
Aschele
C
C
Bertino
J R
JR
D000931:Antidotes / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000008:administration & dosage* / Q000494:pharmacology*; D006801:Humans; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic
D000931:Antidotes; D000964:Antimetabolites, Antineoplastic; D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate