Clinical and pharmacokinetics study of oxaliplatin in colon cancer patients.
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.
Burz
Claudia
C
Department of Immunology, University of Medicine and Pharmacy Iuliu Hatieganu, Romania. cburz@yahoo.fr
Berindan-Neagoe
Ioana Berindan-Neagoe
IB
Balacescu
Ovidiu
O
Tanaselia
Claudiu
C
Ursu
Monica
M
Gog
Adriana
A
Vlase
Laurian
L
Chintoanu
Mircea
M
Balacescu
Loredana
L
Leucuta
Sorin E
SE
Irimie
Alexandru
A
Cristea
Victor
V