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.

Fig. 1

(a) Box and whisker plots of docetaxel clearance in patients who received a single intravenous dose of 75 mg/m² of docetaxel and ABCC2 (left panel) and SLCO1B3 (right panel) genotype. The horizontal lines represent the median values of docetaxel clearance for each genotype. For ABCC2 ?? vs CG/GG rs-12762549, the Wilcoxon–Mann–Whitney rank-sum test (P = 0.048). For the SLCO1B3 AA vs AG/GG rs-11045585, the Wilcoxon–Mann–Whitney rank-sum test (P = 0.799). (b) Box and whisker plots of the nadir absolute neutrophil count (ANC) and ABCC2 rs-12762549 (left panel) and SLCO1B3 rs-11045585 (right panel) genotype. The Wilcoxon–Mann–Whitney rank-sum test (P = 0.861 and 0.922) for the ABCC2 CC vs. CG/GG and SLCO1B3 AA vs. AG/GG genotypes, respectively.