title: Pharmacokinetics and exposure-effect relationships of capecitabine in elderly patients with breast or colorectal cancer.
abstract: OBJECTIVE
  The aims of the present study were (1) to investigate the impact of great age on pharmacokinetics of capecitabine and its metabolites and (2) to evaluate the exposure-effect relationship of capecitabine in elderly patients.
  
  
  METHODS
  Data collected from 20 elderly patients (75-92 years old) with breast or colorectal cancer who received oral capecitabine were analyzed. In order to study the old age effect on pharmacokinetics, data collected from two phase I studies involving 40 younger adults (<75 years old) with metastatic cancer who received oral capecitabine were added in the database. The population pharmacokinetic analysis was based on a four-compartment model describing the sequence of capecitabine and three of its metabolites.
  
  
  RESULTS
  The absorption rate constant was found lower in the oldest patient group (≥75 years) compared with the youngest group, and the constant rate elimination of the 5-fluorouracil metabolite was found decreased over time (i.e., after 2 consecutive weeks of capecitabine administration). This time effect was not found different between the two age groups. In elderly patients, the exposure-safety analysis showed, from the second cycle of chemotherapy, significantly higher median exposures of capecitabine and its metabolites (5'-deoxy-5-fluorocytidine, 5'-deoxy-5-fluorouridine and 5-fluorouracil) in patients who experienced hand-foot syndrome compared with patients who did not.
  
  
  CONCLUSIONS
  This study puts forward new arguments for the treatment of elderly cancer patients who could benefit from capecitabine chemotherapy with acceptable toxicity.
authors.affiliation: UMR-S850, Faculty of Pharmacy, Inserm, 2 Rue Dr Marcland, 87025, Limoges Cedex, France.
authors.forename: Z
authors.initials: Z
authors.lastname: Daher Abdi
authors.forename: S
authors.initials: S
authors.lastname: Lavau-Denes
authors.forename: A
authors.initials: A
authors.lastname: Prémaud
authors.forename: S
authors.initials: S
authors.lastname: Urien
authors.forename: F L
authors.initials: FL
authors.lastname: Sauvage
authors.forename: J
authors.initials: J
authors.lastname: Martin
authors.forename: S
authors.initials: S
authors.lastname: Leobon
authors.forename: P
authors.initials: P
authors.lastname: Marquet
authors.forename: N
authors.initials: N
authors.lastname: Tubiana-Mathieu
authors.forename: A
authors.initials: A
authors.lastname: Rousseau
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil