Department of Immunology, University of Medicine and Pharmacy Iuliu Hatieganu, Romania.
J Gastrointestin Liver Dis. 2009 Mar;18(1):39-43.
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.
评估奥沙利铂的治疗效果，并分析转移性结直肠癌患者游离（未结合）和蛋白结合铂的药代动力学。
60 例 IV 期结肠癌患者接受了 4-6（平均 4.5）个周期的奥沙利铂为基础的联合化疗。评估了反应率、无进展生存期（PFS）和毒性。对 8 例接受 85mg/sqm 或 130mg/sqm 奥沙利铂输注时间为 2-4 小时的患者进行了奥沙利铂药代动力学评估。采用电感耦合等离子体质谱法（ICP-MS）对血液、血浆和血浆超滤物进行药代动力学分析。
总缓解率（完全和部分缓解）为 33 例（55%）。中位进展时间为 9.3 个月。累积神经毒性、呕吐和腹泻、骨髓抑制分别发生在 32.3%、21.3%和 39.4%的患者中。奥沙利铂的平均 Cmax 和 AUC0-24 呈剂量相关性增加。奥沙利铂给药后铂的药代动力学呈三相特征，初始分布相短，终末消除相长。游离铂的清除率相对较高，而血浆和血细胞中铂的清除率相对较低，这可能反映了铂与这些基质的共价结合。
奥沙利铂在晚期结直肠癌患者中具有活性且耐受性良好。具有相对较低的个体间变异性，呈三相消除，平均 Cmax 和 AUC0-24 呈剂量相关性增加。这些结果为奥沙利铂在临床上安全有效使用提供了科学依据。
