title: Clinical and pharmacokinetics study of oxaliplatin in colon cancer patients.
abstract: OBJECTIVE
  to evaluate the therapeutic efficacy of oxaliplatin and to analyze the pharmacokinetics of both ultrafiltrable (free) and protein-bound platinum in patients with metastatic colon cancer.
  
  
  METHODS
  60 patients with stage IV colon carcinoma received 4-6 (mean 4.5) cycles of oxaliplatin based combination chemotherapy. Response rate, progression-free survival (PFS) and toxicity were evaluated. The pharmacokinetics of oxaliplatin was evaluated in 8 patients who were given 85 mg/sqm or 130 mg/sqm using an infusion time of 2-4 h. Pharmacokinetic analysis was performed on blood, plasma and plasma ultrafiltrable by ICP-MS (Inductively Coupled Plasma Mass Spectrometry).
  
  
  RESULTS
  Overall response rate (complete and partial) occurred in 33 (55%) patients. The median time of progression was 9.3 months. Cumulative neurotoxicity, vomiting and diarrhea, myelosuppression appeared in 32.3%, 21.3%, and 39.4% patients, respectively. The mean Cmax and AUC 0-24 of oxaliplatin increased in a dose-related manner. The pharmacokinetics of platinum after oxaliplatin administration was triphasic characterized by a short initial distribution phase and a long terminal elimination phase.The clearance of ultrafiltrable platinum was relatively high and the clearance of platinum from plasma and blood cells was relatively low, which is probably a reflection of the covalent binding of platinum to these matrices.
  
  
  CONCLUSIONS
  Oxaliplatin is active and well tolerated in patients with advanced colon cancer. With a relatively low interpatient variability, it is eliminated triphasically and the mean Cmax and AUC 0-24 increases in a dose-related manner. These results provide a scientific basis for the safe and effective use of oxaliplatin in the clinic.
authors.affiliation: Department of Immunology, University of Medicine and Pharmacy Iuliu Hatieganu, Romania. cburz@yahoo.fr
authors.forename: Claudia
authors.initials: C
authors.lastname: Burz
authors.forename: Ioana Berindan-Neagoe
authors.initials: IB
authors.lastname: Berindan-Neagoe
authors.forename: Ovidiu
authors.initials: O
authors.lastname: Balacescu
authors.forename: Claudiu
authors.initials: C
authors.lastname: Tanaselia
authors.forename: Monica
authors.initials: M
authors.lastname: Ursu
authors.forename: Adriana
authors.initials: A
authors.lastname: Gog
authors.forename: Laurian
authors.initials: L
authors.lastname: Vlase
authors.forename: Mircea
authors.initials: M
authors.lastname: Chintoanu
authors.forename: Loredana
authors.initials: L
authors.lastname: Balacescu
authors.forename: Sorin E
authors.initials: SE
authors.lastname: Leucuta
authors.forename: Alexandru
authors.initials: A
authors.lastname: Irimie
authors.forename: Victor
authors.initials: V
authors.lastname: Cristea