Abstract
Abstract Background Interindividual variability of pharmacokinetics may account for unpredictable toxicity of docetaxel. Pharmacogenetic analysis on the metabolic pathway of docetaxel has been performed in hopes of identifying predicting factors related to docetaxel-related toxicities. Methods From March 2007 to June 2008, female patients with early-stage breast cancer receiving docetaxel-containing adjuvant chemotherapy were included in this study. The 4 cycles of planned dose of docetaxel (100 mg/m2) was performed as adjuvant chemotherapy, following 4 cycles of adriamycin and cyclophosphamide. We evaluated toxicity profile of docetaxel according to the drug-metabolizing enzyme or transporter polymorphisms reported to affect the pharmacokinetics of docetaxel. The single nucleotide polymorphisms (SNPs) of CYP3A5 gene (6986 A>G), ABCB1 gene (1236 C>T, 3435 C>T, 2677 G>T(A)), ABCC2 gene (-24C>T, 1249 G>A, 3972 C>T, rs1276549) and SCLO1B3 gene (334 T>G, 699 G>A, rs11045585) were sequenced from individuals. Toxicities including neutropenia was evaluated for the 1st cycle of docetaxel and defined according to the NCI CTCAE version 3.0. Results Pharmacogenetic analysis was performed in 218 Korean women who had received the planned chemotherapy. With regard to ABCB1 3435 C>T, ABCB1 3435 T/T had significantly higher risks of neutropenia (P=0.015). Meanwhile, allele frequencies for CYP3A5 6986 G and ABCB1 3435 T revealed a trend for neutropenia (P=0.107 and 0.068). We could not find any other association between genotypes and other toxicities. Discussion Although ABCB1 3435 T/T was significantly associated with docetaxel-related neutropenia in our study population, polymorphism of pharmacogenetic genes related to docetaxel metabolism did not appear to be evidently associated with docetaxel-related adverse events. Further external validation of these genes may be required to allow them to enter clinical practice. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-15-03.
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