The relationship of polymorphisms in ABCC2 and SLCO1B3 with docetaxel pharmacokinetics and neutropenia: CALGB 60805 (Alliance)

Lionel D. Lewis, Antonius A. Miller, Kouros Owzar, Robert Bies, Svetlana Markova, Chen Jiang, Deanna L. Kroetz, Merrill J. Egorin, Howard L. McLeod, Mark J. Ratain

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Docetaxel-related neutropenia was associated with polymorphisms in the drug transporters ABCC2 and SLCO1B3 in Japanese cancer patients. We hypothesized that this association is because of reduced docetaxel clearance, associated with polymorphisms in those genes. We studied 64 US cancer patients who received a single cycle of 75 mg/m of docetaxel monotherapy. We found that the ABCC2 polymorphism at rs-12762549 trended to show a relationship with reduced docetaxel clearance (P=0.048), but not with neutropenia. There was no significant association of the SLCO1B3 polymorphisms with docetaxel clearance or neutropenia. We conclude that the relationship between docetaxel-associated neutropenia and polymorphisms in drug transporters identified in Japanese patients was not confirmed in this cohort of US cancer patients.

Original languageEnglish (US)
Pages (from-to)29-33
Number of pages5
JournalPharmacogenetics and Genomics
Volume23
Issue number1
DOIs
StatePublished - Jan 2013
Externally publishedYes

Fingerprint

docetaxel
Neutropenia
Pharmacokinetics
Neoplasms
Pharmaceutical Preparations

Keywords

  • ABCC2 (pharmacogenetics)
  • docetaxel
  • neutropenia
  • pharmacokinetics
  • SLCO1B3

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)

Cite this

The relationship of polymorphisms in ABCC2 and SLCO1B3 with docetaxel pharmacokinetics and neutropenia : CALGB 60805 (Alliance). / Lewis, Lionel D.; Miller, Antonius A.; Owzar, Kouros; Bies, Robert; Markova, Svetlana; Jiang, Chen; Kroetz, Deanna L.; Egorin, Merrill J.; McLeod, Howard L.; Ratain, Mark J.

In: Pharmacogenetics and Genomics, Vol. 23, No. 1, 01.2013, p. 29-33.

Research output: Contribution to journalArticle

Lewis, LD, Miller, AA, Owzar, K, Bies, R, Markova, S, Jiang, C, Kroetz, DL, Egorin, MJ, McLeod, HL & Ratain, MJ 2013, 'The relationship of polymorphisms in ABCC2 and SLCO1B3 with docetaxel pharmacokinetics and neutropenia: CALGB 60805 (Alliance)', Pharmacogenetics and Genomics, vol. 23, no. 1, pp. 29-33. https://doi.org/10.1097/FPC.0b013e32835b16d8
Lewis, Lionel D. ; Miller, Antonius A. ; Owzar, Kouros ; Bies, Robert ; Markova, Svetlana ; Jiang, Chen ; Kroetz, Deanna L. ; Egorin, Merrill J. ; McLeod, Howard L. ; Ratain, Mark J. / The relationship of polymorphisms in ABCC2 and SLCO1B3 with docetaxel pharmacokinetics and neutropenia : CALGB 60805 (Alliance). In: Pharmacogenetics and Genomics. 2013 ; Vol. 23, No. 1. pp. 29-33.
@article{cfb8b379b6cf48b38ecdb2d342fcd218,
title = "The relationship of polymorphisms in ABCC2 and SLCO1B3 with docetaxel pharmacokinetics and neutropenia: CALGB 60805 (Alliance)",
abstract = "Docetaxel-related neutropenia was associated with polymorphisms in the drug transporters ABCC2 and SLCO1B3 in Japanese cancer patients. We hypothesized that this association is because of reduced docetaxel clearance, associated with polymorphisms in those genes. We studied 64 US cancer patients who received a single cycle of 75 mg/m of docetaxel monotherapy. We found that the ABCC2 polymorphism at rs-12762549 trended to show a relationship with reduced docetaxel clearance (P=0.048), but not with neutropenia. There was no significant association of the SLCO1B3 polymorphisms with docetaxel clearance or neutropenia. We conclude that the relationship between docetaxel-associated neutropenia and polymorphisms in drug transporters identified in Japanese patients was not confirmed in this cohort of US cancer patients.",
keywords = "ABCC2 (pharmacogenetics), docetaxel, neutropenia, pharmacokinetics, SLCO1B3",
author = "Lewis, {Lionel D.} and Miller, {Antonius A.} and Kouros Owzar and Robert Bies and Svetlana Markova and Chen Jiang and Kroetz, {Deanna L.} and Egorin, {Merrill J.} and McLeod, {Howard L.} and Ratain, {Mark J.}",
year = "2013",
month = "1",
doi = "10.1097/FPC.0b013e32835b16d8",
language = "English (US)",
volume = "23",
pages = "29--33",
journal = "Pharmacogenetics and Genomics",
issn = "1744-6872",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - The relationship of polymorphisms in ABCC2 and SLCO1B3 with docetaxel pharmacokinetics and neutropenia

T2 - CALGB 60805 (Alliance)

AU - Lewis, Lionel D.

AU - Miller, Antonius A.

AU - Owzar, Kouros

AU - Bies, Robert

AU - Markova, Svetlana

AU - Jiang, Chen

AU - Kroetz, Deanna L.

AU - Egorin, Merrill J.

AU - McLeod, Howard L.

AU - Ratain, Mark J.

PY - 2013/1

Y1 - 2013/1

N2 - Docetaxel-related neutropenia was associated with polymorphisms in the drug transporters ABCC2 and SLCO1B3 in Japanese cancer patients. We hypothesized that this association is because of reduced docetaxel clearance, associated with polymorphisms in those genes. We studied 64 US cancer patients who received a single cycle of 75 mg/m of docetaxel monotherapy. We found that the ABCC2 polymorphism at rs-12762549 trended to show a relationship with reduced docetaxel clearance (P=0.048), but not with neutropenia. There was no significant association of the SLCO1B3 polymorphisms with docetaxel clearance or neutropenia. We conclude that the relationship between docetaxel-associated neutropenia and polymorphisms in drug transporters identified in Japanese patients was not confirmed in this cohort of US cancer patients.

AB - Docetaxel-related neutropenia was associated with polymorphisms in the drug transporters ABCC2 and SLCO1B3 in Japanese cancer patients. We hypothesized that this association is because of reduced docetaxel clearance, associated with polymorphisms in those genes. We studied 64 US cancer patients who received a single cycle of 75 mg/m of docetaxel monotherapy. We found that the ABCC2 polymorphism at rs-12762549 trended to show a relationship with reduced docetaxel clearance (P=0.048), but not with neutropenia. There was no significant association of the SLCO1B3 polymorphisms with docetaxel clearance or neutropenia. We conclude that the relationship between docetaxel-associated neutropenia and polymorphisms in drug transporters identified in Japanese patients was not confirmed in this cohort of US cancer patients.

KW - ABCC2 (pharmacogenetics)

KW - docetaxel

KW - neutropenia

KW - pharmacokinetics

KW - SLCO1B3

UR - http://www.scopus.com/inward/record.url?scp=84871918938&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871918938&partnerID=8YFLogxK

U2 - 10.1097/FPC.0b013e32835b16d8

DO - 10.1097/FPC.0b013e32835b16d8

M3 - Article

C2 - 23188068

AN - SCOPUS:84871918938

VL - 23

SP - 29

EP - 33

JO - Pharmacogenetics and Genomics

JF - Pharmacogenetics and Genomics

SN - 1744-6872

IS - 1

ER -