Pharmacology of oxaliplatin in solid tumor patients with hepatic dysfunction: A preliminary report of the national cancer institute organ dysfunction working group

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

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Oxaliplatin, which was recently approved by the US Food and Drug Administration for the treatment of advanced colorectal cancer, is often administered to patients with altered liver function caused by hepatic metastases. Because of the absence of data on the clearance of oxaliplatin in patients with liver dysfunction, and to develop dosing recommendations for the safe use of oxaliplatin in this clinical setting, the Organ Dysfunction Working Group of the National Cancer Institute performed a phase I and pharmacokinetic trial of this drug in patients displaying a wide range of liver function abnormalities. Sixty patients grouped into five classes of liver function were enrolled in this study, including a 12-patient control group with normal liver function, 15 patients with "mild," 16 patients with "moderate," and 16 with "severe" liver dysfunction, as well as one patient who had undergone liver transplantation. The patients had a median age of 62 years and a Eastern Cooperative Oncology Group performance status of 0. All patients had received prior systemic chemotherapy, and 70% had a diagnosis of a gastrointestinal malignancy. The control patients were treated with 130 mg/m2 oxaliplatin intravenously every 21 days; the starting doses for patients with mild, moderate, or severe liver dysfunction or post-liver transplantation were 105, 80, or 60 mg/m2, respectively. Cohorts of three or more patients were escalated from these starting doses to 130 mg/m2 if dose-limiting toxicities were not observed, and pharmacokinetic evaluations were performed at each dose level for every category of liver dysfunction. We found that oxaliplatin was well tolerated at its recommended dose and schedule of 130 mg/m2 every 21 days in patients with all levels of liver dysfunction, and that there was no apparent alteration in the clearance of either total or ultrafilterable platinum species from plasma, even in patients with severe hepatic functional abnormalities.

Original languageEnglish (US)
Pages (from-to)14-19
Number of pages6
JournalSeminars in Oncology
Volume30
Issue number4 SUPPL. 15
StatePublished - Aug 2003
Externally publishedYes

Fingerprint

oxaliplatin
National Cancer Institute (U.S.)
Pharmacology
Liver
Neoplasms
Liver Diseases
Liver Transplantation

ASJC Scopus subject areas

  • Oncology

Cite this

Pharmacology of oxaliplatin in solid tumor patients with hepatic dysfunction : A preliminary report of the national cancer institute organ dysfunction working group. / Doroshow, James H.; Synold, Timothy W.; Gandara, David; Mani, Sridhar; Remick, Scot C.; Mulkerin, Daniel; Hamilton, Anne; Sharma, Sunil; Ramanathan, Ramesh K.; Lenz, Heinz Josef; Graham, Martin; Longmate, Jeffrey; Takimoto, Chris H.; Ivy, Percy.

In: Seminars in Oncology, Vol. 30, No. 4 SUPPL. 15, 08.2003, p. 14-19.

Research output: Contribution to journalArticle

Doroshow, JH, Synold, TW, Gandara, D, Mani, S, Remick, SC, Mulkerin, D, Hamilton, A, Sharma, S, Ramanathan, RK, Lenz, HJ, Graham, M, Longmate, J, Takimoto, CH & Ivy, P 2003, 'Pharmacology of oxaliplatin in solid tumor patients with hepatic dysfunction: A preliminary report of the national cancer institute organ dysfunction working group', Seminars in Oncology, vol. 30, no. 4 SUPPL. 15, pp. 14-19.
Doroshow, James H. ; Synold, Timothy W. ; Gandara, David ; Mani, Sridhar ; Remick, Scot C. ; Mulkerin, Daniel ; Hamilton, Anne ; Sharma, Sunil ; Ramanathan, Ramesh K. ; Lenz, Heinz Josef ; Graham, Martin ; Longmate, Jeffrey ; Takimoto, Chris H. ; Ivy, Percy. / Pharmacology of oxaliplatin in solid tumor patients with hepatic dysfunction : A preliminary report of the national cancer institute organ dysfunction working group. In: Seminars in Oncology. 2003 ; Vol. 30, No. 4 SUPPL. 15. pp. 14-19.
@article{331a8511f5394e408919ac2229418a3f,
title = "Pharmacology of oxaliplatin in solid tumor patients with hepatic dysfunction: A preliminary report of the national cancer institute organ dysfunction working group",
abstract = "Oxaliplatin, which was recently approved by the US Food and Drug Administration for the treatment of advanced colorectal cancer, is often administered to patients with altered liver function caused by hepatic metastases. Because of the absence of data on the clearance of oxaliplatin in patients with liver dysfunction, and to develop dosing recommendations for the safe use of oxaliplatin in this clinical setting, the Organ Dysfunction Working Group of the National Cancer Institute performed a phase I and pharmacokinetic trial of this drug in patients displaying a wide range of liver function abnormalities. Sixty patients grouped into five classes of liver function were enrolled in this study, including a 12-patient control group with normal liver function, 15 patients with {"}mild,{"} 16 patients with {"}moderate,{"} and 16 with {"}severe{"} liver dysfunction, as well as one patient who had undergone liver transplantation. The patients had a median age of 62 years and a Eastern Cooperative Oncology Group performance status of 0. All patients had received prior systemic chemotherapy, and 70{\%} had a diagnosis of a gastrointestinal malignancy. The control patients were treated with 130 mg/m2 oxaliplatin intravenously every 21 days; the starting doses for patients with mild, moderate, or severe liver dysfunction or post-liver transplantation were 105, 80, or 60 mg/m2, respectively. Cohorts of three or more patients were escalated from these starting doses to 130 mg/m2 if dose-limiting toxicities were not observed, and pharmacokinetic evaluations were performed at each dose level for every category of liver dysfunction. We found that oxaliplatin was well tolerated at its recommended dose and schedule of 130 mg/m2 every 21 days in patients with all levels of liver dysfunction, and that there was no apparent alteration in the clearance of either total or ultrafilterable platinum species from plasma, even in patients with severe hepatic functional abnormalities.",
author = "Doroshow, {James H.} and Synold, {Timothy W.} and David Gandara and Sridhar Mani and Remick, {Scot C.} and Daniel Mulkerin and Anne Hamilton and Sunil Sharma and Ramanathan, {Ramesh K.} and Lenz, {Heinz Josef} and Martin Graham and Jeffrey Longmate and Takimoto, {Chris H.} and Percy Ivy",
year = "2003",
month = "8",
language = "English (US)",
volume = "30",
pages = "14--19",
journal = "Seminars in Oncology",
issn = "0093-7754",
publisher = "W.B. Saunders Ltd",
number = "4 SUPPL. 15",

}

TY - JOUR

T1 - Pharmacology of oxaliplatin in solid tumor patients with hepatic dysfunction

T2 - A preliminary report of the national cancer institute organ dysfunction working group

AU - Doroshow, James H.

AU - Synold, Timothy W.

AU - Gandara, David

AU - Mani, Sridhar

AU - Remick, Scot C.

AU - Mulkerin, Daniel

AU - Hamilton, Anne

AU - Sharma, Sunil

AU - Ramanathan, Ramesh K.

AU - Lenz, Heinz Josef

AU - Graham, Martin

AU - Longmate, Jeffrey

AU - Takimoto, Chris H.

AU - Ivy, Percy

PY - 2003/8

Y1 - 2003/8

N2 - Oxaliplatin, which was recently approved by the US Food and Drug Administration for the treatment of advanced colorectal cancer, is often administered to patients with altered liver function caused by hepatic metastases. Because of the absence of data on the clearance of oxaliplatin in patients with liver dysfunction, and to develop dosing recommendations for the safe use of oxaliplatin in this clinical setting, the Organ Dysfunction Working Group of the National Cancer Institute performed a phase I and pharmacokinetic trial of this drug in patients displaying a wide range of liver function abnormalities. Sixty patients grouped into five classes of liver function were enrolled in this study, including a 12-patient control group with normal liver function, 15 patients with "mild," 16 patients with "moderate," and 16 with "severe" liver dysfunction, as well as one patient who had undergone liver transplantation. The patients had a median age of 62 years and a Eastern Cooperative Oncology Group performance status of 0. All patients had received prior systemic chemotherapy, and 70% had a diagnosis of a gastrointestinal malignancy. The control patients were treated with 130 mg/m2 oxaliplatin intravenously every 21 days; the starting doses for patients with mild, moderate, or severe liver dysfunction or post-liver transplantation were 105, 80, or 60 mg/m2, respectively. Cohorts of three or more patients were escalated from these starting doses to 130 mg/m2 if dose-limiting toxicities were not observed, and pharmacokinetic evaluations were performed at each dose level for every category of liver dysfunction. We found that oxaliplatin was well tolerated at its recommended dose and schedule of 130 mg/m2 every 21 days in patients with all levels of liver dysfunction, and that there was no apparent alteration in the clearance of either total or ultrafilterable platinum species from plasma, even in patients with severe hepatic functional abnormalities.

AB - Oxaliplatin, which was recently approved by the US Food and Drug Administration for the treatment of advanced colorectal cancer, is often administered to patients with altered liver function caused by hepatic metastases. Because of the absence of data on the clearance of oxaliplatin in patients with liver dysfunction, and to develop dosing recommendations for the safe use of oxaliplatin in this clinical setting, the Organ Dysfunction Working Group of the National Cancer Institute performed a phase I and pharmacokinetic trial of this drug in patients displaying a wide range of liver function abnormalities. Sixty patients grouped into five classes of liver function were enrolled in this study, including a 12-patient control group with normal liver function, 15 patients with "mild," 16 patients with "moderate," and 16 with "severe" liver dysfunction, as well as one patient who had undergone liver transplantation. The patients had a median age of 62 years and a Eastern Cooperative Oncology Group performance status of 0. All patients had received prior systemic chemotherapy, and 70% had a diagnosis of a gastrointestinal malignancy. The control patients were treated with 130 mg/m2 oxaliplatin intravenously every 21 days; the starting doses for patients with mild, moderate, or severe liver dysfunction or post-liver transplantation were 105, 80, or 60 mg/m2, respectively. Cohorts of three or more patients were escalated from these starting doses to 130 mg/m2 if dose-limiting toxicities were not observed, and pharmacokinetic evaluations were performed at each dose level for every category of liver dysfunction. We found that oxaliplatin was well tolerated at its recommended dose and schedule of 130 mg/m2 every 21 days in patients with all levels of liver dysfunction, and that there was no apparent alteration in the clearance of either total or ultrafilterable platinum species from plasma, even in patients with severe hepatic functional abnormalities.

UR - http://www.scopus.com/inward/record.url?scp=0141993765&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141993765&partnerID=8YFLogxK

M3 - Article

C2 - 14523790

AN - SCOPUS:0141993765

VL - 30

SP - 14

EP - 19

JO - Seminars in Oncology

JF - Seminars in Oncology

SN - 0093-7754

IS - 4 SUPPL. 15

ER -