Dose-escalating and pharmacologic study of oxaliplatin in adult cancer patients with impaired hepatic function: a National Cancer Institute Organ Dysfunction Working Group study.

Dose-escalating and pharmacologic study of oxaliplatin in adult cancer patients with impaired hepatic function: a National Cancer Institute Organ Dysfunction Working Group study. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Dose-escalating and pharmacologic study of oxaliplatin in adult cancer patients with impaired hepatic function: a National Cancer Institute Organ Dysfunction Working Group study. Abstract Text:

Timothy W Synold,Chris H Takimoto,James H Doroshow,David 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, ,

PURPOSE: To determine the toxicities, pharmacokinetics, and maximally tolerated doses of oxaliplatin in patients with hepatic impairment 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 to 130 mg/m(2) 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 hepatic dysfunction: control group A [bilirubin, AST, and AP < or = upper limit of normal (ULN)], mild dysfunction group B (bilirubin < or = ULN, ULN < AST < or = 2.5 x ULN, or ULN < AP < or = 5 x ULN), moderate dysfunction group C (ULN < bilirubin < or = 3.0 mg/dL, AST > 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/m(2) was well tolerated in all cohorts. Platinum clearance did not correlate with any liver function test. Two of 56 assessable patients with 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.

Dose-escalating and pharmacologic study of oxaliplatin in adult cancer patients with impaired hepatic function: a National Cancer Institute Organ Dysfunction Working Group study. Publishing Authors By Initials

TW Synold,CH Takimoto,JH Doroshow,D Gandara,S Mani,SC Remick,DL Mulkerin,A Hamilton,S Sharma,RK Ramanathan,HJ Lenz,M Graham,J Longmate,BM Kaufman,P Ivy, ,

For similar organic chemicals: organometallic compounds: organoplatinum compounds research abstracts see: organic chemicals: organometallic compounds: organoplatinum compounds research

PUBMED ID PMID:

MEDLINE DATE:

Dose-escalating and pharmacologic study of oxaliplatin in adult cancer patients with impaired hepatic function: a National Cancer Institute Organ Dysfunction Working Group study. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Clinical cancer research : an official journal of

VOLUME: 13

Page Numbers: 3660-6

Journal Abbreviation: Clin. Cancer Res.

ISSN: 1078-0432

DAY: 15

MONTH: Jun

YEAR: 2007

Dose-escalating and pharmacologic study of oxaliplatin in adult cancer patients with impaired hepatic function: a National Cancer Institute Organ Dysfunction Working Group study. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9502500

Dose-escalating and pharmacologic study of oxaliplatin in adult cancer patients with impaired hepatic function: a National Cancer Institute Organ Dysfunction Working Group study. Keywords Mesh Terms:

KEYWORDS: Organoplatinum Compounds

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Dose-escalating and pharmacologic study of oxaliplatin in adult cancer patients with impaired hepatic function: a National Cancer Institute Organ Dysfunction Working Group study. Information

Substance Name: oxaliplatin

Registry Number: 63121-00-6

Grant and Affiliation Information for Dose-escalating and pharmacologic study of oxaliplatin in adult cancer patients with impaired hepatic function: a National Cancer Institute Organ Dysfunction Working Group study.

AFFILIATION: City of Hope Comprehensive Cancer Center, Duarte, California, USA.

Country: United States

AGENCY: United States NCI

GRANT: U01CA076642

ACRONYM: CA

MEDLINETA: Clin Cancer Res

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Dose-escalating and pharmacologic study of oxaliplatin in adult cancer patients with impaired hepatic function: a National Cancer Institute Organ Dysfunction Working Group study Related Publications

• A study of lipotropic factors derived from the pancreas.
• A two-tiered quality management program: Morbidity and Mortality conference data applied to resident education.
• Assay of secretin and cholecystokinin concentrates.
• Banthine in the treatment of peptic ulcer.
• Benign hyperplasia of the mandibular condyle; report of an additional case, with suggestion for simplified operative technique.
• Dose-escalating and pharmacologic study of oxaliplatin in adult cancer patients with impaired hepatic function: a National Cancer Institute Organ Dysfunction Working Group study.
• Effect of diet on liver regeneration in partially hepatectomized rats.
• Effect of gold administration on liver function in dogs.
• FES Cycling Improves CNS Status and Decreases Metabolic Risk Factors in SCI Individuals: 1751: Board #39 May 31 9:00 AM 10:30 AM.
• Further studies on the effect of continuous intragastric infusion of acid and pepsin in dogs.
• Glucuronic acid and cinchophen ulcer.
• Incidence of the blood groups and the secretor factor in patients with pernicious anemia and stomach carcinoma.
• Medical research; operation humanity.
• Nazi war crimes of a medical nature; some conclusions.
• Preliminary report of a clinical trial of orally administered hog duodenum powder in the treatment of chronic ulcerative colitis.
• Production of gastroduodenal ulcers in the dog by continuous subcutaneous or intravenous administration of histamine.
• Relation of rate of gastric evacuation to time of onset of gastric hunger contractions.
• Resuscitation from obstructive asphyxia.
• Role of blood sugar levels in spontaneous and insulin-induced hunger in man.
• Stimulating effect of sugar, fat, and meat meals on duodenal secretion in the dog.
• Ten public health aspects of BCG vaccination.
• The carcinogenicity of fat "browned" by heating.
• The chronic typhoid carrier; the effect of cholecystectomy on the bacteriologic course.
• The inhalation of 1-(3',4'-dihydroxyphenyl)-2-isopropylaminoethanol (norisodrine sulfate dust).
• The lower uterine segment; its derivation and physiologic behavior.
• The repair of full-thickness cheek defects following irradiation necrosis.
• Thermal irritation in gastric disease.
• Work at high altitude; the effect of diet and other factors on the rise of lactic and pyruvic acids, and the lactate-pyruvate ratio in human subjects at simulated high altitudes.
• Work at high altitude; the relation between daily oral intake and excretion of thiamin and riboflavin.
• Work at high altitude; utilization of thiamin and riboflavin at low and high dietary intake; effect of work and rest.