P2.01-058 Pharmacokinetic Parameter Variability of Docetaxel between Individuals and Its Relationship with Hematological Toxicity

Abstract

Docetaxel is the commonly used chemotherapy drugs of various types of tumors. However, the major adverse effect of which is the dose-limiting hematologic toxicity. In clinical practice, 3/4 grade neutropenia and febrile (FN) is the severe side effects threatening the patient life. This research aims to analyze the variability of docetaxel’s medicine area under the curve (AUC) between individuals and its relationship with hematological toxicity in advanced NSCLC, which sets up the mathematical model to predict its hematological toxicity by docetaxel AUC to lay the theoretical foundation for individual adjustment in future. Select 32 patients with advanced NSCLC in Shandong Cancer Hospital that receiving docetaxel chemotherapy treatment from 2014-10 to 2015-12. Adopt Mycare® reagent kit to determine the blood concentration, and calculate the docetaxel AUC over model software of non-mixed effects. After standardized treatment, analyze the AUC variability between individuals, relationship of AUC with decreased amount of neutrophils before or after the chemotherapy, and the relationship of AUC with 3/4 grade neutropenia. And make the fitting with different methods to set up the mathematical model in relationship with decreased percentage of neutrophils after AUC prediction chemotherapy and incidence rate of 3/4 grade neutropenia. 1. The AUC of 32 patients in the first cycle after standardized treatment that use docetaxel is between 1.8ug.h/ml-4.7ug.h/ml in average of 3.32±0.12ug.h/ml. The difference between the maximum value and minimum one is 2.6 times. 2. AUC value has the tendency that increases as cycle number increases. However, the number of chemotherapy cycle has no statistical significance of AUC influence (F=0.186, P=0.824). 3. The model predicting the decreased percentage of neutrophils with docetaxel AUC is : y1 = 1.4812x2 + 3.0217x + 29.061 (cycle 1), y2 = 4.3981x2 + 14.006x + 50.532 (cycle 2), y3 = 2.0683x2 + 2.1257x + 19.604(cycle 3), y4 = 4.683x2 - 19.273 + 61.398 (cycle 4); The model predicting the incidence rate of 3/4 grade neutrophils is y=19.383ln(x)+2.4005. (x=AUC). This research sets up the mathematical model to predict the decreased percentage of neutrophils and incidence rate of 3/4 grade neutropenia by docetaxel AUC, which provides basis for screening high-risk patients who may suffer seriously hematological toxicity and lay the theoretical foundation for individualized adjustment based on doxetaxel AUC. In addition, as the first cycle of doxetaxel AUC has important reference value, it suggests that all patients receiving docetaxel chemotherapy at the first time must receive AUC test.