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Dose Versus pharmacokinetics for predicting tolerance to 5‐day continuous infusion of 5‐FU
Author(s) -
Milano G.,
Roman P.,
Khater R.,
Frenay M.,
Renee N.,
Namer M.
Publication year - 1988
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910410411
Subject(s) - pharmacokinetics , toxicity , medicine , therapeutic index , colorectal cancer , continuous infusion , pharmacology , fluorouracil , pharmacodynamics , maximum tolerated dose , urology , anesthesia , chemotherapy , drug , cancer
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/m 2 , and by a systemic intravenous route (i.v.) at doses ranging from 650 to 1,300 mg/m 2 . 5‐FU blood levels were available for a total of 179 cycles. Toxicity was dose‐de pendent during h.i.a. cycles but not during i.v. cycles. For h.i.a. cycles, 1,000 mg/m 2 /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.