Klin Farmakol Farm. 2011;25(2):87-91

Comments on 5-fluorouracil - based anticancer chemotherapy innovations

Jiřina Martínková¹, Miloš Hroch¹, Jiří Grim²

¹ Ústav farmakologie, Karlova Univerzita v Praze, Lékařská fakulta v Hradci Králové

² Onkologická klinika, Fakultní nemocnice, Hradec Králové

5-fluorouracil (5-FU) is used for adjuvant (postoperative) and neoadjuvant (preoperative) cytostatic therapy. Dose is determined by body

surface (mg/m2) in spite of the fact that a linear relationship between the dose and systemic clearance has not been proven so far. A good

message is kinetically guided approach for adjuvant therapy, which focuses on 5-FU pharmacokinetic monitoring followed by individual

dose adjustment. This strategy confined to 5-FU i. v. infusion was proven to be more effective in ensuring an appropriate treatment course

with minimized toxicity and optimized therapeutic outcome. The target exposure (AUC- area under the curve of plasma concentration

obtained since the infusion has been started) is defined, determining therapeutic efficacy and acceptable risks of treatment – induced

toxicity. 5-FU pharmacokinetic profiles from midcycle AUCs enable dose adjustment in later treatment cycles using a limited sampling

strategy. Midcycle AUCs reveal subjects at high risk of toxicity caused by a low drug systemic clearance. This outcome was obtained

from phase II-III studies with their selected patients but routine clinical use is made possible by the existing body of data, providing

practical guidelines for target parameters and dose adjustment charts. Neoadjuvant therapy is based on 5-FU additive contribution to

radiotherapy effects (radiochemotherapy), but there are no data informing about a relationship between the 5-FU dose/kinetics and

its effects (therapeutic/toxicity).

Keywords: 5-fluorouracil, kinetically guided individualized therapy, adjuvant therapy, neoadjuvant therapy

Published: June 20, 2011  Show citation