TY - JOUR
T1 - Dose-escalating and pharmacologic study of oxaliplatin in adult cancer patients with impaired hepatic function
T2 - A national cancer institute organ dysfunction working group study
AU - Synold, Timothy W.
AU - Takimoto, Chris H.
AU - Doroshow, James H.
AU - Gandara, David
AU - Mani, Sridhar
AU - Remick, Scot C.
AU - Mulkerin, Daniel L.
AU - Hamilton, Anne
AU - Sharma, Sunil
AU - Ramanathan, Ramesh K.
AU - Lenz, Heinz Josef
AU - Graham, Martin
AU - Longmate, Jeffrey
AU - Kaufman, Bennett M.
AU - Ivy, Percy
PY - 2007/6/15
Y1 - 2007/6/15
N2 - Purpose: To determine the toxicities, pharmacokinetics, and maximally tolerated doses of oxaliplatin in patientswith hepaticimpairment and to develop formal guidelines for oxaliplatin dosing in this patient population. Experimental Design: Sixty adult cancer patients with variable hepatic function received i.v. oxaliplatin ranging from 60 to130 mg/m2 every 3 weeks. Patients were stratified by levels of total bilirubin, aspartate aminotransferase (AST), and alkaline phosphatase (AP) into five cohorts based on the degree of hepaticdy sfunction: control group A [bilirubin, AST, and AP ≤ upper limit of normal (ULN)], mild dysfunction group B (bilirubin V ULN, ULN ≤ AST V 2.5 x ULN, or ULN < AP ≤ 5 x ULN), moderate dysfunction group C (ULN < 2.5 x ULN, or AP > 5 x ULN), severe dysfunction group D (bilirubin > 3.0 mg/dL, any AST, and any AP), and liver transplantation group E (any bilirubin, any AST, and any AP). Doses were escalated in cohorts of three patients, and urine and plasma ultrafiltrates were assayed for platinum concentrations. Results: Dose escalation of single-agent oxaliplatin to 130 mg/m2 was well tolerated in all cohorts. Platinum clearance did not correlate with any liver function test. Two of 56 assessable patientswith a diagnosis of laryngeal carcinoma and cervical adenocarcinoma experienced partial responses lasting 3 and 5.5 months. Conclusions: Oxaliplatin at 130 mg/m 2 every 3 weeks was well tolerated in all patients with impaired liver function. Dose reductions of single-agent oxaliplatin are not indicated in patients with hepatic dysfunction.
AB - Purpose: To determine the toxicities, pharmacokinetics, and maximally tolerated doses of oxaliplatin in patientswith hepaticimpairment and to develop formal guidelines for oxaliplatin dosing in this patient population. Experimental Design: Sixty adult cancer patients with variable hepatic function received i.v. oxaliplatin ranging from 60 to130 mg/m2 every 3 weeks. Patients were stratified by levels of total bilirubin, aspartate aminotransferase (AST), and alkaline phosphatase (AP) into five cohorts based on the degree of hepaticdy sfunction: control group A [bilirubin, AST, and AP ≤ upper limit of normal (ULN)], mild dysfunction group B (bilirubin V ULN, ULN ≤ AST V 2.5 x ULN, or ULN < AP ≤ 5 x ULN), moderate dysfunction group C (ULN < 2.5 x ULN, or AP > 5 x ULN), severe dysfunction group D (bilirubin > 3.0 mg/dL, any AST, and any AP), and liver transplantation group E (any bilirubin, any AST, and any AP). Doses were escalated in cohorts of three patients, and urine and plasma ultrafiltrates were assayed for platinum concentrations. Results: Dose escalation of single-agent oxaliplatin to 130 mg/m2 was well tolerated in all cohorts. Platinum clearance did not correlate with any liver function test. Two of 56 assessable patientswith a diagnosis of laryngeal carcinoma and cervical adenocarcinoma experienced partial responses lasting 3 and 5.5 months. Conclusions: Oxaliplatin at 130 mg/m 2 every 3 weeks was well tolerated in all patients with impaired liver function. Dose reductions of single-agent oxaliplatin are not indicated in patients with hepatic dysfunction.
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U2 - 10.1158/1078-0432.CCR-06-2385
DO - 10.1158/1078-0432.CCR-06-2385
M3 - Article
C2 - 17575231
AN - SCOPUS:34250784654
SN - 1078-0432
VL - 13
SP - 3660
EP - 3666
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 12
ER -