Clinical and pharmacokinetics study of oxaliplatin in colon cancer patients.

Department of Immunology, University of Medicine and Pharmacy Iuliu Hatieganu, Romania.
Journal of gastrointestinal and liver diseases: JGLD (Impact Factor: 2.2). 04/2009; 18(1):39-43.
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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.
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).
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.
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.

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    • "First, IC50 values for L-OHP in this study correspond approximately to the peak plasma concentration after intravenous infusion (Cmax) in clinical setting, and Cmax is thought to be important for efficacy, considering that antitumor activity of L-OHP is concentration and time dependent [32,33] and infusion time of L-OHP is almost fixed as 2 hours except in some cases with high risk of toxicity. Second, interpatient variability in L-OHP pharmacokinetics, evaluated as ultrafiltrable platinum, is moderate to low and 4-fold change is above interpatient variability in Cmax, indicating that this magnitude of change in sensitivity is unignorable [31,34,35]. "
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    ABSTRACT: Objectives To evaluate the presence and severity of oxaliplatin-associated neurotoxicity in clinical practice and the clinical management of this adverse side effect.
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