The Analysis Of Related Factors Of Docetaxel AUC And Toxic Side Effects In Patients With Cervical Cancer

PurposeIn the context of precision medicine,this study monitored the blood Concentration of patients with cervical cancer treated with docetaxel and calculated the pharmacokinetic parameters,the Area Under concentration-Tine Curve(AUC).The correlation between AUC and body surface area,administration dose,AUC and toxic and side effects was analyzed.The relationship between chemotherapy efficacy and pharmacokinetics and the optimal dose range of docetaxel for patients were discussed.MethodsThis study included patients with stage IB1-ⅡA1 cervical squamous cell carcinoma initially diagnosed in***from 2017 to 2019(no preoperative and postoperative radiotherapy,no preoperative neoadjuvant chemotherapy,and no other systemic serious diseases).All 90 patients received docetaxel+nedaplatin chemotherapy regimen,with an interval of 21 days as one chemotherapy cycle,and the treatment information of 4 chemotherapy courses was counted.The first chemotherapy dose was calculated according to the BSA method,and the subsequent dose was dynamically adjusted according to the area under the blood concentration curve(AUC)of docetaxel.Blood samples were collected at two time points to monitor the blood concentration:blood samples were collected 0-10 minutes before the end of DTX infusion.Monitoring blood sample 2:Collection within 30-60 minutes after DTX infusion.The AUC value was calculated by the automatic biochemical analyzer and the Mycare DtX kit,and the toxic and side effects were evaluated on the third day of chemotherapy.Statistical software was used to analyze the correlation between the dose used and the area under the blood concentration curve(AUC)of docetaxel and the toxic and side effects of chemotherapy.Results:AUC is closely related to leukopenia after chemotherapy.The higher the AUC value,the greater the probability and degree of leukopenia.AUC has no obvious correlation with the decrease of hemoglobin after chemotherapy.Because patients take blood tonic drugs routinely during chemotherapy,the conclusion of this data is of little significance.AUC is closely related to thrombocytopenia after chemotherapy.The higher the AUC value,the greater the probability and degree of thrombocytopenia.AUC is closely related to the decrease of neutrophils after chemotherapy.The higher the AUC value,the greater the probability and degree of neutrophil decrease.AUC is closely related to abnormal liver function after chemotherapy.The higher the AUC value,the greater the probability and degree of abnormal liver function.The range of AUC of the 327 cycle data for 90 cervical cancer patients was 1.1-7.2 mg·h/L,2.44 mg·h/L,mean The standard deviation is 0.8537,The coefficient of variation among individuals was 34.86%;The AUC range of plasma concentration parameters in chemotherapy for 263 cycles of blood toxicity mg·h/L,1.2-7.2 Average mg·h/L,3.22 The standard deviation is 0.8397,A reference limit of 2.4223 and a limit of 4.01 for AUC with hematotoxicity in 95%of patients 17.Toxicity reference range mg·h/L.2.4223-4.0117The AUC range of blood concentration parameters in chemotherapy was 1.1-7.2 mg`h/L,according to the surface area method mg·h/L,median 2.8 2.78 mg-h/L,mean The standard deviation is 0.8317,The coefficient of variation was 29.9.The range of blood concentration parameters AUC in chemotherapy for patients who adjust the dosage according to the blood concentration parameters mg·h/L,1.2-4.8 2.3 mg·h/L,Medium 2.25 mg·h/L.mean The standard deviation is 0.6378,The coefficient of variation is 28.3.Statistical software analysis found that the correlation coefficients of body surface area,age,administration dose and AUC were r=0.156,Pr=0.129,r=0.105,0.293,r=0.142,and 0.242,respectively.according to the level of ar=0.05,the hypothesis test could not exclude the possibility that the correlation coefficient was equal to 0.there was no correlation between body surface area,age,administration dose and AUC value.Conclusions1.There was no statistically significant correlation between AUC and patient surface area,age,dose.2.In the chemotherapy cycle,the blood drug concentration parameter AUC ranged from 1.2 to 7.2,with a mean value of 3.22 and a standard deviation of 0.8397,The lower limit and upper limit of AUC for 95%of patients with hemotoxicity were 2.7024 and 3.7351 respectively,and the toxicity reference range was 2.4223-4.0177mg·h/L.3.According to the body surface area method,the blood drug concentration parameter AUC in the chemotherapy of the patients was 1.1-7.2mg·h/L,the mean value was 2.78mg·h/L,the standard deviation was 0.8317,and the coefficient of variation was 29.9%.For patients who adjusted the dose according to the blood drug concentration parameter AUC,the blood drug concentration parameter AUC in chemotherapy ranged from 1.2-4.8mg·h/L,with an average of 2.25mg·h/L.The standard deviation was 0.6378 and the coefficient of variation was 28.3%.The pharmacokinetic parameter AUC of docetaxel was significantly different among individuals,and the blood concentration was higher and the variation rate was higher according to the way of BSA administration,which needed to be improved.Therefore,the AUC value measured in chemotherapy can be used to guide the dose of the next chemotherapy drug.