Docetaxel exposure and hematological toxicity in Chinese patients with locally advanced/metastatic nasopharyngeal carcinoma.

Ting Mei, Xin An, Jing Zhan, Kunyao Feng, Hai Liao, Chong Zhao, Su Li

International journal of clinical pharmacology and therapeutics 2021 Mar

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This study aimed to describe the area under the plasma concentration-time curve (AUC) and the relationship with hematological toxicity plus clinical responses of docetaxel in patients with nasopharyngeal carcinoma. Furthermore, a suitable docetaxel exposure level would be identified to guide clinical dosing. 96 patients with locally advanced or metastatic nasopharyngeal carcinoma treated with docetaxel-based chemotherapy were enrolled. Docetaxel was measured by turbidimetric immunoassay. Associations between docetaxel exposure and hematologic toxicity, effect, and recurrence time were analyzed. Receiver operating characteristic curve analysis was performed to determine an optimal AUC value to predict the decrease in absolute neutrophil counts. Interpatient variability was large with regard to exposure (AUC) and clearance. The AUC values of 76 patients in course 1 varied more than 4 fold (3.17 ± 0.84 µg×h/mL, ranging from 1.4 to 6.0 µg×h/mL). Clearance was 42.8 L/h (ranging from 20.8 to 73.7 L/h) with ~ 3-fold interindividual variability. The incidence of grade 3/4 leukopenia, 3/4 neutropenia, and febrile neutropenia was 46.3, 85.2, and 13.5%, respectively, in course 1. Docetaxel exposure was the only significant predictor (p < 0.001) of severe toxicity, including grade 4 neutropenia and febrile neutropenia. A cutoff value of 2.85 µg×h/mL was selected as the target AUC. Higher AUC values were not observed to be associated with better drug effect. The dose was calculated based on individual clearance and a target AUC of 2.85 µg×h/mL, helping to adjust the next cycle of doses and solve interpatient variability.

Citation

Ting Mei, Xin An, Jing Zhan, Kunyao Feng, Hai Liao, Chong Zhao, Su Li. Docetaxel exposure and hematological toxicity in Chinese patients with locally advanced/metastatic nasopharyngeal carcinoma. International journal of clinical pharmacology and therapeutics. 2021 Mar;59(3):216-223