Individual 5FU-dose adaptation schedule using bimonthly pharmacokinetically modulated LV5FU2 regimen: A feasibility study in patients with advanced colorectal cancer

Aim of the study: SFU-dose adaptation optimal schedule using bimonthly LV5F U2 regimen was modulated by previously validated individual pharmacokinetic parameters, in 38 patients with advanced colorectal cancer. Methods: At th e 1st cure, 5F-U pharmacokinetic parameters (particularly the area under cu rve (AUC) in mg.h/l.m(2)) were calculated in all patients. In 19 patients ( A), 5FU infusion doses were progressively increased from 25 to 50 % (at eve ry cycle), according to AUC levels from 2nd to 6th; in 19 consecutive patie nts (B), 5FU infusion doses were increased, at the same time, at the 2nd cu re, according to a protocol taking in account AUC at the Ist cure: increase of 150 % if 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 +/- 3.215 (range from 3.9 to 16.41). Large interindividual variability was observed b) FU in fusion 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 2 3 (per cycle) occurred not very frequently (8 % haematological, 6 % dige stive and 2 % cutaneous toxicity) and remained acceptable. Conclusion: This feasibility study established a SFU-dose intensification optimal strategy within the bimonthly LV5FU2 schedule with a control for the risk of toxicit y. This study constitutes the basis for a multicentre phase II trial to eva luate the importance of this approach in terms of efficacy and survival.