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

J Chemother. 2010 Jun;22(3):179-85. doi: 10.1179/joc.2010.22.3.179.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antimetabolites, Antineoplastic / pharmacokinetics
  • Area Under Curve
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / secondary
  • Dose-Response Relationship, Drug
  • Female
  • Fluorouracil / administration & dosage*
  • Fluorouracil / pharmacokinetics
  • Humans
  • Infusions, Intravenous
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Prospective Studies
  • Retrospective Studies
  • Survival Rate
  • Tissue Distribution
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • Fluorouracil