TY - JOUR
T1 - Dose-escalating and pharmacological study of oxaliplatin in adult cancer patients with impaired renal function
T2 - A National Cancer Institute organ dysfunction working group study
AU - Takimoto, Chris H.
AU - Remick, Scot C.
AU - Sharma, Sunil
AU - Mani, Sridhar
AU - Ramanathan, Ramesh K.
AU - Doroshow, James
AU - Hamilton, Anne
AU - Mulkerin, Daniel
AU - Graham, Martin
AU - Lockwood, Graham F.
AU - Ivy, Percy
AU - Egorin, Merrill
AU - Schuler, Barbara
AU - Greenslade, Denis
AU - Goetz, Andrew
AU - Knight, Ronald
AU - Thomas, Rebecca
AU - Monahan, Brian P.
AU - Dahut, William
AU - Grem, Jean L.
PY - 2003/7/15
Y1 - 2003/7/15
N2 - Purpose: This study was undertaken to determine the toxicities, pharmacokinetics, and maximum tolerated doses of oxaliplatin in patients with renal impairment and to develop formal guidelines for oxaliplatin dosing in this patient population. Patients and Methods: Thirty-seven adult cancer patients with variable renal function received intravenous oxaliplatin at 60 to 130 mg/m2 every 3 weeks. Patients were stratified by 24-hour creatinine clearance (CrCL) into four cohorts: group A (controls, CrCL ≥60 mL/min), group B (mild dysfunction, CrCL 40 to 59 mL/min), group C (moderate dysfunction, CrCL 20 to 39 mL/min), and group D (severe dysfunction, CrCL <20 mL/min). Doses were escalated in cohorts of three patients, and urine and plasma ultrafiltrates were assayed for platinum concentrations. Results: No dose-limiting toxicities were observed in any patient group during the first cycle of therapy. Escalation of oxaliplatin to the maximum dose of 130 mg/m 2 was well tolerated in all patient groups with a CrCL ≥20 mL/min (groups A, B, and C). Pharmaeokinetic analysis showed that patients with decreased CrCL had a corresponding decrease in the clearance of plasma ultrafiltrable platinum (r2 = 0.765). However, oxaliplatin-induced side effects were not more common or severe in patients with mild to moderate renal dysfunction, despite the decrease in ultrafiltrable platinum clearance. Conclusion: Oxaliplatin at 130 mg/m2 every 3 weeks is well tolerated by patients with mild to moderate degrees of renal dysfunction. These data strongly support the recommendation that dose reductions of single-agent oxaliplatin are not necessary in patients with a CrCL greater than 20 mL/min.
AB - Purpose: This study was undertaken to determine the toxicities, pharmacokinetics, and maximum tolerated doses of oxaliplatin in patients with renal impairment and to develop formal guidelines for oxaliplatin dosing in this patient population. Patients and Methods: Thirty-seven adult cancer patients with variable renal function received intravenous oxaliplatin at 60 to 130 mg/m2 every 3 weeks. Patients were stratified by 24-hour creatinine clearance (CrCL) into four cohorts: group A (controls, CrCL ≥60 mL/min), group B (mild dysfunction, CrCL 40 to 59 mL/min), group C (moderate dysfunction, CrCL 20 to 39 mL/min), and group D (severe dysfunction, CrCL <20 mL/min). Doses were escalated in cohorts of three patients, and urine and plasma ultrafiltrates were assayed for platinum concentrations. Results: No dose-limiting toxicities were observed in any patient group during the first cycle of therapy. Escalation of oxaliplatin to the maximum dose of 130 mg/m 2 was well tolerated in all patient groups with a CrCL ≥20 mL/min (groups A, B, and C). Pharmaeokinetic analysis showed that patients with decreased CrCL had a corresponding decrease in the clearance of plasma ultrafiltrable platinum (r2 = 0.765). However, oxaliplatin-induced side effects were not more common or severe in patients with mild to moderate renal dysfunction, despite the decrease in ultrafiltrable platinum clearance. Conclusion: Oxaliplatin at 130 mg/m2 every 3 weeks is well tolerated by patients with mild to moderate degrees of renal dysfunction. These data strongly support the recommendation that dose reductions of single-agent oxaliplatin are not necessary in patients with a CrCL greater than 20 mL/min.
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U2 - 10.1200/JCO.2003.11.015
DO - 10.1200/JCO.2003.11.015
M3 - Article
C2 - 12860942
AN - SCOPUS:0042631396
SN - 0732-183X
VL - 21
SP - 2664
EP - 2672
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 14
ER -