The Analysis Of Relative Factors Of AUC And The Toxicity Of Docetaxel In The Breast Cancer Patients

[Objective]As the same as other chemotherapy drugs,docetaxel is also administered based on the standard body surface area(BSA)dosing.Due to the highly variable individuals,unpredictable toxicity and ineffective therapy is very common.To reduce incidence of toxicity and improve the efficiency,we used an immunoassay(PETIA)that measured plasma docetaxel concentration and reported an AUC in mg·h/L.We'll discuss the relationship between AUC and BSA,AUC and BMI,AUC and the dose,AUC and the cycles,the AUC of individual difference and the correlation between AUC and toxicity.[Methods]Ninety-six breast cancer patients(thirty-seven patients from Shenzhen People's hospital and fifty-nine patients from commercial data base)administered chemotherapy with the TC(T:docetaxel,C:Cyclophosphamide),every 21 days as a cycle.Blood samples were collected before 10 mins ending infusion of docetaxel and after 30 mins ending infusion of docetaxel in one of cycles to detect the serum concentration of docetaxel and calculate AUC value.The toxicity of the chemotherapy was evaluated on the 5th day the 7th day and the 9th day after the chemotherapy.The relationship between AUC and BSA,AUC and BMI,AUC anddose,AUC and the cycles were analyzed using statistical method.The AUC of individual difference was also analyzed by the statistical method.The incidence of toxicity was analyzed in AUC<2.5mg·h/L group and AUC?2.5mg·h/L group.[Results](1)There were no significant differences in the AUC value in the different ages,BSA,BMI and dose.(P>0.05)(2)Grouping by age,there were no significant difference in the Individual AUC.Grouping by the cycles,there were no significant difference in the AUC in each cycle.(3)Thirty-seven data from the Shenzhen people's Hospital was used to analyze the relationship between AUC and toxicity.The result showed that the incidence of neutropenia and leukopenia of 1-2 grade and 3-4 grade was lower in the AUC<2.5mg·h/L group than that in the AUC?2.5mg·h/L group.(P<0.05).The thrombocytopenia and anemia of 1-2 grade was lower in the AUC<2.5mg·h/L group than that in the AUC?2.5mg·h/L group.(P<0.05)We can't compare with thrombocytopenia and anemia of 3-4 grade and liver dysfunction between the two group.[Conclusion]Docetaxel is an ideal candidate for PK dose optimization.The pharmacokinetic parameter AUC is obviously correlated with sever neutropenia and leukopenia of 3-4grade and maintaining docetaxel AUC within 2.5mg·h/L could reduce hematological adverse reaction in breast cancer patients receiving 3-week docetaxel chemotherapy.