Dose-escalating and pharmacologic study of oxaliplatin in adult cancer patients with impaired hepatic function: A national cancer institute organ dysfunction working group study

Timothy W. Synold, Chris H. Takimoto, James H. Doroshow, David R Gandara, Sridhar Mani, Scot C. Remick, Daniel L. Mulkerin, Anne Hamilton, Sunil Sharma, Ramesh K. Ramanathan, Heinz Josef Lenz, Martin Graham, Jeffrey Longmate, Bennett M. Kaufman, Percy Ivy

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3660-3666
Number of pages7
JournalClinical Cancer Research
Volume13
Issue number12
DOIs
StatePublished - Jun 15 2007

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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