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Journal of Chinese Pharmaceutical Sciences ›› 2016, Vol. 25 ›› Issue (7): 512-516.DOI: 10.5246/jcps.2016.07.056

• Original articles • Previous Articles     Next Articles

Pharmacokinetically determined docetaxel exposure as a predictor of hematologic toxicity in Chinese patients with early stage breast cancer

Fang Wang, Zhuo Chen, Lin Li, Mingzhi Zhu, Youyi Xiong, Yuanting Gu*   

  1. Department of Breast Surgery 2, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
  • Received:2016-03-25 Revised:2016-04-15 Online:2016-07-19 Published:2016-05-15
  • Contact: Tel.: +86-13703844321, E-mail: rxwkgyt@163.com

Abstract:

Neutropenia is the major dose-limiting toxicity in patients being treated with docetaxel. The purpose of this study was to evaluate the relationship between pharmacokinetically determined docetaxel exposures and grade 34 hematologic toxicity (neutropenia and leukopenia) in Chinese breast cancer patients.Patients received docetaxel infusions (75 mg/m2 over 1 h) once every 3 weeks. At the first cycle, a patient’s docetaxel exposure was determined as an area under the curve (AUC) using plasma concentrations of docetaxel measured at two different time points (at the end of the infusion and 30–60 min later). Pharmacokinetic studies and toxicity assessments were performed for 61 patients. Grade 34 neutropenia occurred in 34 (55.7%) patients, and grade 34 leukopenia occurred in 30 (49.2%) patients. Individual exposure to docetaxel was highly variable (AUC range = 1.06.2 mg·h/L, inter-individual CV = 39.6%). There was a significant difference in the mean docetaxel AUC by grade of toxicity for both neutropenia and leukopenia. The average AUC for low (0–2) and high grade (3–4) neutropenia was 2.0 and 2.8 mg·h/L, respectively (P = 0.001), and for leukopenia was 1.9 and 2.9 mg·h/L, respectively (P<0.0001). Individual exposure to docetaxel is variable and predictive of high grade hematologic toxicity. The optimal docetaxel AUC to maximize efficacy and minimize toxicity in Chinese breast cancer patients merits further investigation.

Key words: Docetaxel, AUC, Toxicity, Breast cancer, Pharmacokinetics/pharmacodynamics

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