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

  • Author(s): Lewis, Lionel D
  • Miller, Antonius A
  • Owzar, Kouros
  • Bies, Robert R
  • Markova, Svetlana
  • Jiang, Chen
  • Kroetz, Deanna L
  • Egorin, Merrill J
  • McLeod, Howard L
  • Ratain, Mark J
  • Alliance for Clinical Trials in Oncology
  • et al.

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.

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