乳腺癌患者多西他赛稳态AUC与骨髓抑制相关性安全窗探索

Safety Window Study on Correlation Between Docetaxel Homeostasis AUC and Myelosuppression in Breast Cancer Patients

目的:多西他赛治疗窗窄,个体间药代动力学差异大,本课题拟通过前瞻性研究,明确多西他赛稳态药时曲线下面积(AUC)在乳腺癌患者中的安全窗及稳态AUC与骨髓抑制发生的相关性。方法:选择2019年6月~2021年6月经病理诊断为乳腺癌Ⅰ~Ⅲ期的辅助化疗或新辅助化疗患者101例,测定、计算并分析多西他赛稳态AUC。结果:多西他赛安全窗参考范围为稳态AUC 1~1.6 mg·h·L^(-1),此范围内并未发现严重骨髓抑制情况,Ⅰ~Ⅱ度骨髓抑制发生率为15.9%;当参考范围介于1.7~2.5 mg·h·L^(-1)时,骨髓抑制发生率为21.4%,其中严重骨髓抑制发生率为14.2%;当参考范围介于2.6~3.0 mg·h·L^(-1)时,骨髓抑制发生率为66.7%。多西他赛稳态AUC 1~1.6 mg·h·L^(-1)的患者使用与未使用粒细胞刺激因子者之间骨髓抑制发生率并无显著差异(P>0.05)。结论:多西他赛安全窗参考范围为稳态AUC 1~1.6 mg·h·L^(-1),在此参考范围内,患者可考虑无需预防性使用粒细胞刺激因子。

Objective:To determine the therapeutic window AUC in breast cancer patients and discuss on its correlation with myelosuppression through retrospective analysis.Methods:A total of 101 breast cancer patients pathologically diagnosed as stageⅠ-Ⅲreceiving adjuvant or neoadjuvant chemotherapy during June 2019 to June 2021 were selected.The AUC values of docetaxel were calculated by the Mycare software and statistically analyzed.Results:When the therapeutic window reference range was 1-1.6 mg·h·L^(-1),no severe myelosuppression was found and the incidence rate ofⅠ-Ⅱdegree myelosuppression was 15.9%.When the reference range was 1.7-2.5 mg·h·L^(-1),the incidence of myelosuppression was 21.4%,with severe myelosuppression at 14.2%.When the reference range was 2.5-3.0 mg·h·L^(-1),the incidence of myelosuppression was 66.7%.In addition,there was no significant difference between the prophylactic administration of granulocyte stimulating factor and the non-prophylactic application for patients within the reference range of 1-1.6 mg·h·L^(-1)(P>0.05).Conclusion:The optimal treatment window reference range of docetaxel is 1-1.6 mg·h·L^(-1),within which patients need no prophylaxis with granulocyte-stimulating factor.