期刊
ANNALS OF TRANSLATIONAL MEDICINE
卷 8, 期 5, 页码 -出版社
AME PUBL CO
DOI: 10.21037/atm.2020.01.76
关键词
Docetaxel; area under time-concentration curve (AUC); Chinese; head and neck cancer (HNC); ncutropenia
资金
- Medical Scientific Research Foundation of Guangdong Province of China [A2018010]
- National Nature Science Foundation of China [81572659, 81602011]
Background: Area under time-concentration curve (AUC) of docetaxel is related with its toxicity and efficacy. The aim of this study is to investigate the target range of docetaxel AUC in Chinese head and neck cancer (HNC) patients. Methods: Eligible HNC patients were enrolled and received at least 2 cycles of docetaxel-based chemotherapy. A simplified pharmacokinetic (PK) strategy (2 monitored samples) was developed to simulate docetaxel AUC using the nonlinear mixed-effect modelling program. Preliminary target range of AUC was pre-set as 2.5-3.7 mu g.hr/mL according to fx)oled analysis from 8 previous studies. Fisher exact test was used to analyze the relationship between AUC with neutropenia and efficacy, and to verify the target range. Results: Thirty-nine eligible patients were enrolled. Grade 3-4 and grade 4 neutropenia rate in 1st cycle was 64% and 36%, respectively. AUC simulation by simplified PK strategy was acceptable compared to full sampling method from the analysis of archived 3(X) patients' data, with -5.67% of mean prediction error (MPE). Median AUC of all patients was 2.58 mu g.hr/mL (range from 1.28 to 9.39). A significant correlation (P=0.007) was detected between AUC and body surface area (BSA)-dosage, but BSA contributed only 18.3% of AUC inter-individual variability. Docetaxel AUC was significantly related with the severity (grade 3-4) of neutropenia (correlation of coefficient was 0.452, P=0.004). Fourteen patients (36%) were within the target AUC range. Patients with AUC above the target experienced more severe neutropenia (grade 3-4 rate 100% vs. 56%, P=0.036; grade 4 rate 86% vs. 25%, P=0.005). No significant difference of response rate was found between patients within the target or not. Conclusions: A simplified samples PK strategy was developed for docetaxel AUC simulation. The target range of docetaxel AUC in Chinese HNC patients was suggested at 2.5-3.7 mu g.hr/mL for reduced toxicity without compromising efficacy of docetaxel treatment.
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