Safety Window Study on Correlation Between Docetaxel Steady-State AUC and Myelosuppression in Breast Cancer Patients

Oct 1, 2023·

Yunyun Xu

Lujuan Cao

Bingxue Xie

Corresponding Author

Ying Yao

Wenbo Yuan

Zihong Lu

Sunmin Jiang

Di Yin

Dongxu Wang

· 1 min read

PDF DOI

Abstract

Objective: To determine the therapeutic window AUC in breast cancer patients and discuss on its correlation with myelosuppression through prospective analysis. Methods: A total of 101 breast cancer patients pathologically diagnosed as stage I-III receiving 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 of grade I-II 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 14.3%. When the reference range was 2.6-3.0 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 may not require prophylactic use of granulocyte colony-stimulating factor.

Type

Journal article

Publication

Pharmaceutical and Clinical Research, 31(5), 425-429

Key Findings

Established docetaxel safety window at steady-state AUC 1-1.6 mg·h·L⁻¹
No severe myelosuppression (grade III-IV) observed within the safety window
Inter-individual AUC variability exceeded 3-fold (CV% > 29%) despite BSA-based dosing
Statistically significant difference in severe myelosuppression between AUC ≤1.6 and ≥1.7 mg·h·L⁻¹ groups (P = 0.017)
No significant benefit of prophylactic G-CSF for patients within the safety window (P = 0.693)

Significance

This prospective study provides evidence for personalized docetaxel dosing in breast cancer chemotherapy through therapeutic drug monitoring, potentially reducing unnecessary G-CSF prophylaxis and associated adverse effects while maintaining treatment efficacy.