Impact of polymorphisms on docetaxel-induced neutropenia in Japanese patients with gynecologic cancer.

Abstract

e13015 Background: Docetaxel is a key drug for the treatment of patients with gynecologic cancer. However, docetaxel-induced neutropenia, which may occur as a result of individual genetic variation, is a significant side effect of this therapy. In this study, we examined the correlation between previously reported single nucleotide polymorphisms (SNPs), rs12762549 in ABCC2 and rs11045585 in SLCO1B3, rs2740574 in CYP3A4, rs776746 in CYP3A5 and severe docetaxel-induced neutropenia in a population comprising gynecologic cancer patients who were treated with a docetaxel-contained combination therapy. Methods: Fifty-one gynecologic cancer patients treated with docetaxel were genotyped. Of these, 46 patients were treated with a combination of docetaxel and carboplatin and 5 with a combination of docetaxel and gemcitabine. We performed the TaqMan SNP genotyping assay to evaluate SNPs in ABCC2 and SLCO1B3. The DMET Plus genotyping platform (DMET) was used to evaluate other SNPs. Results: The reported scoring system using ABCC2 and SLCO1B3 did not show any significant correlation with severe neutropenia due to docetaxel. When we focused on the 42 patients treated with DC combination therapy, the homozygotes either rs12762549 in ABCC2 or rs776746 in CYP3A5 are significantly predominant in the 19 patients having grade 4 neutropenia. Conclusions: Our results suggest that the risk of severe neutropenia among Japanese gynecologic cancer patients treated with DC might be predicted by genotyping SNPs of ABCC2 and CYP3A5.