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Medline ® Abstract for Reference 25

of 'Fluoropyrimidine-associated cardiotoxicity: Incidence, clinical manifestations, mechanisms, and management'

25
TI
Individual 5FU-dose adaptation schedule using bimonthly pharmacokinetically modulated LV5FU2 regimen: a feasibility study in patients with advanced colorectal cancer.
AU
Ychou M, Duffour J, Pinguet F, Kramar A, Joulia JM, Topart D, Bressolle F
SO
Anticancer Res. 1999 May-Jun;19(3B):2229-35.
 
AIM OF THE STUDY: SFU-dose adaptation optimal schedule using bimonthly LV5FU2 regimen was modulated by previously validated individual pharmacokinetic parameters, in 38 patients with advanced colorectal cancer.
METHODS: At the 1st cure, 5F-U pharmacokinetic parameters (particularly the area under curve (AUC) in mg.h/l.m2) were calculated in all patients. In 19 patients (A), 5FU infusion doses were progressively increased from 25 to 50% (at every cycle), according to AUC levels from 2nd to 6th; in 19 consecutive patients (B), 5FU infusion doses were increased, at the same time, at the 2nd cure, according to a protocol taking in account AUC at the 1st cure: increase of 150% it AUC<5, of 100% if 5<AUC<10, of 50% if 10<AUC<15, of 25% if 15<AUC<20 in case of toxicity<grade 3.
RESULTS: a) AUC in all patients, at the beginning of the treatment averaged 9.05 +/- 3.115 (range from 3.9 to 16.41). Large interindividual variability was observed. b) FU infusion doses at the 2nd cure, increased 40% in group A and 82% in group B. Corresponding AUC increased respectively of 42% and 96%. 3-WHO toxicity 23 (per cycle) occurred not very frequently (8% haematological, 6% digestive and 2% cutaneous toxicity) and remained acceptable.
CONCLUSION: This feasibility study established a 5FU-dose intensification optimal strategy within the bimonthly LV5FU2 schedule with a control for the risk of toxicity. This study constitutes the basis for a multicentre phase II trial to evaluate the importance of this approach in terms of efficacy and survival.
AD
Unit of Digestive Oncology, CRLC Val d'Aurelle, Parc Euromédecine, Montpellier, France.
PMID