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


CONCLUSIONS
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.
Ychou
M
M
Unit of Digestive Oncology, CRLC Val d'Aurelle, Parc Euromédecine, Montpellier, France.
Duffour
J
J
Pinguet
F
F
Kramar
A
A
Joulia
J M
JM
Topart
D
D
Bressolle
F
F
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000097:blood; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012004:Rectal Neoplasms / Q000188:drug therapy*; D012811:Sigmoid Neoplasms / Q000188:drug therapy
D002955:Leucovorin; D005472:Fluorouracil