Dose versus pharmacokinetics for predicting tolerance to 5-day continuous infusion of 5-FU.
This non-randomized study reports pharmaco-clinical data on 5-FU administered by the widely used 5-day continuous infusion schedule to 42 patients with metastatic colorectal cancer; 5-FU was given by hepatic intra-arterial route (h.i.a.) at doses ranging from 800 to 1,450 mg/m2, and by a systemic intravenous route (i.v.) at doses ranging from 650 to 1,300 mg/m2. 5-FU blood levels were available for a total of 179 cycles. Toxicity was dose-dependent during h.i.a. cycles but not during i.v. cycles. For h.i.a. cycles, 1,000 mg/m2/day represented the threshold dose for tolerance. The individual total cycle drug concentration-time product might predict toxicity for both i.v. and h.i.a. cycle when the threshold is set at 30,000 ng/ml.hr. These data may be of practical value for improving the therapeutic index of 5-day continuous treatment by 5-FU given by i.v. or h.i.a. routes.
Milano
G
G
Laboratory of Pharmacokinetics, Centre Antoine Lacassagne, Nice, France.
Roman
P
P
Khater
R
R
Frenay
M
M
Renee
N
N
Namer
M
M
D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged
D005472:Fluorouracil