Published in:
01-05-2006 | Original Paper
Clinical pharmacokinetics of oxaliplatin and 5-fluorouracil administered in combination with leucovorin in Korean patients with advanced colorectal cancer
Authors:
Hea-Kyoung Cho, Eun-Sook Lee, Jung-Won Lee, Jong-Kook Park, Jin-Hyoung Kang, Kyung-Shik Lee, Chang-Koo Shim, Suk-Jae Chung, Dae-Duk Kim, Hyo-Jeong Kuh
Published in:
Journal of Cancer Research and Clinical Oncology
|
Issue 5/2006
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Abstract
Purpose: Oxaliplatin and 5-fluorouracil (5-FU) act synergistically in colorectal cancer. Here, we evaluated the pharmacokinetics of oxaliplatin and 5-FU administered in combination with leucovorin in Korean advanced colorectal cancer patients. Methods: Nine patients with advanced colorectal cancer were included in this study. The 3-week regimen consisted of oxaliplatin (2-h infusion, 130 mg/m2 on day 1) followed by 5-FU and leucovorin (2-h infusion, 425 and 20 mg/m2, respectively, from day 1 to day 5). Blood samples were taken and platinum concentrations in total plasma, plasma ultrafiltrate, and RBCs were determined. Plasma concentrations of 5-FU were also determined. Results: The C
max of oxaliplatin was observed at the end of infusion, with mean values of 4.66, 0.84, and 2.69 μg/ml for total plasma, plasma ultrafiltrate, and RBC samples, respectively. C
max ratios of total/free were significantly higher than those reported in other ethnic groups. An accumulation of platinum was observed in RBCs, but not in total plasma and plasma ultrafiltrate samples. A significant correlation was found between the total body clearance of ultrafiltrable platinum and creatinine clearance. The C
max of plasma 5-FU ranged from 23.9 to 533.8 ng/ml, indicating large inter-patient pharmacokinetic variations. Conclusions: This study shows that pharmacokinetics of oxaliplatin in Korean patients is comparable with that of other ethic groups, except for the higher C
max ratios of total/free. The C
max of 5-FU in plasma showed large variations among patients. Antitumor efficacy in Korean advanced colorectal cancer patients given oxaliplatin and 5-FU should be further evaluated with respect to pharmacokinetic variabilities.