| Objective:To analyze and compare recent efficacy. CA125Index changes and toxic side effects of different doses of carboplatin plus paclitaxel in advanced ovarian cancer patients:to establish the detection method of blood concentration of carboplatin in vivo by HPLC. and to measure the pharmacokinetic parameters in vivo between different dosage of carboplatin in two regimens by intravenous infusion, to guide rational drug use and individual therapy with carboplatin.Methods:1. A total of84patients screened with advanced (Ⅲ and Ⅳ) epithelial ovarian cancer from ovarian cancer patients treated in Tianjin Medical University Cancer Institute and Hospital between September2009to September2011were retrospectively analyzed. All patients received ovarian cytoreductive surgery and the postoperative pathologic examination confirmed primary epithelial ovarian cancer. The AUC of carboplatin according to the dose and creatinine value was calculated. These84patients were divided into the observation group (Group B.5≤AUC<7.31cases) and the control group (Group A.3≤AUC<5.53cases). Recent efficacy. CA125Index changes and toxic side effects after more than two normal courses were analyzed according to the standard of WHO.2. The HPLC-UV assay was developed. Ten eligible patients with advanced epithelial ovarian cancer were treated with different doses of carboplatin (AUC=4and AUC=6) plus paclitaxel. respectively, with5patients in each group. After intravenous infusion of2h. the plasma concentration of platinum at0h,0.5h,1h,2h,4h,8h,16h,24h was determined using uridine as the internal standard. C-T curve was drawn and pharmacokinetic parameters of two groups were calculated. The Kromasil C-18column (250mm×4.6mm.5μm) was used, the mobile phase was H2O, the flow rate was1mL/min. the detection wavelength was230nm. the sample size was50μL. and the column temperature was30℃Results:1.①For paclitaxel combined with carboplatin3≤AUC<5chemotherapy, the total response rate (CR+PR) of the53cases was47.1%:for paclitaxel combined with carboplatin5≤AUC<7chemotherapy, the total response rate (CR+PR) of the31cases was58.1%. χ2test showed no significant difference between the two groups (P>0.05).②After chemotherapy, dropped CA125levels below normal level (35U/mL for the normal threshold) were observed in35patients of Group A (66.0%) and28patients of Group B(90.3%). χ2test showed a significant difference between the two groups (P<0.05).③The incidence of blood platelet count reduction of Group B was higher than that of Group A (P<0.05). but no significant differences were found in white blood cell count reducion. hemoglobin reduction and neutrophils reduction (P>0.05). The two groups had no significant difference in gastrointestinal reaction, neurotoxicity. liver and kidney toxicity or cardiovascular toxicity incidence (P>0.05).2. The plasma concentration of carboplatin presented a good linear correlation within the range1.56-100μg/mL and regression equation was y=11.3150x-0.2760.(R=0.9990). The relative recovery of carboplatin was98.91%and RSD equaled to3.96%. Pharmacokinetic parameters of AUC(0-t). AUC(0-∞) MRT(0-t). VRT(0-∞). and Cmaxvand K10after once administration were significantly different between the two groups (P<0.05).Conclusions:1. Although the paclitaxel plus carboplatin3≤AUC<5(Group A) chemotherapy and paclitaxel plus carboplatin5≤AUC<7(Group B) chemotherapy had no significant difference on recent efficacy, there was a tendency that the efficacy in Group B was higher than that in Group A. The degree of serum CA125reduction was higher in Group B than in Group A. Group B had a higher incidence of blood platelet count reduction than Group A. With the dose increase, the toxicity increased but was still in a manageable range. When AUC reached more than seven, the adverse drug reaction can not be tolerated.2. The established method to determine carboplatin in vivo is simple, sensitive and accurate. The pharmacokinetic parameters of carboplatin are dose-related. Carboplatin can give full play to its action in the condition of AUC=6. |
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