Clinical impact of intesified 5-Fluorouracil-based chemotherapy using a prospective pharmacokinetically-guided dosing approach: comparative study in elderly and non-elderly patients with metastatic colorectal cancer.
We compared clinical outcome and pharmacokinetic (pK) parameters of a new pharmacokinetically-guided dosing strategy in two groups of patients (age < or >65 years) with metastatic colorectal cancer (mCRC). We retrospectively analyzed all the patients with mCRC, receiving standard LV5FU2 regimen during cycle-1, intensified from cycle-2 onwards according to an adaptation schedule based on the area under the concentration-time curve (AUC) value (mg.h/l.m(2)) of 5-FU measured during cycle-1. Among the 103 eligible patients, the 48 elderly (median age 70 range 65-80) did not differ significantly from the 55 non-elderly patients (median age 59 range 33-64) in pPK parameters (including AUC at cycle-1 and cycle-2), efficacy (objective response rate of 27% [16.1-40.9] in younger and 35% [22.2-50.5] in older patients, p = 0.4) and tolerability (33.3% of overall grade 3-4 toxicities in older patients and 34.5% in younger, p = 0.9). Our data indicated high dose-intensity values, not significantly different between elderly and non-elderly patients. it was feasible to increase the 5-fU continuous infusion dose in 43/55 (78%) younger and 40/48 (83%) older patients (p=0.509) and even to double it in half of the patients of both groups. Aging did not seem to limit intensified chemotherapy or to affect the pK behavior of the 5-FU.
Duffour
J
J
Department of Digestive Oncology, Val d'Aurelle Regional Cancer Center Montpellier Cedex, France. jduffour@valdorel.fnclcc.fr
Roca
L
L
Bressolle
F
F
Abderrahim
A G
AG
Poujol
S
S
Pinguet
F
F
Ychou
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D007262:Infusions, Intravenous; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D015996:Survival Rate; D014018:Tissue Distribution; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil