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

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 3-4 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 3-4 neutropenia occurred in 34 （55.7%） patients, and grade 3-4 leukopenia occurred in 30 （49.2%） patients. Individual exposure to docetaxel was highly variable （AUC range = 1.0-6.2 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 ,4 UC 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.