| Ovarian cancer is the fifth leading cause of cancer death in women,and advanced epithelial ovarian cancer(EOC)is the most lethal gynecological malignancy.In China,the incidence of ovarian cancer is 5.4 per 100,000,while the five-year survival rate of the FIGO i-iv ovarian cancer is 90.2%,68.3%,32.9%,and 16.1%respectively,and the pathogenesis of ovarian cancer is still unclear.Carboplatin and paclitaxel is the first line of advanced ovarian cancer chemotherapy,and the clinical commonly used IHPC in the treatment of advanced ovarian cancer patients with ascites,but the drug dose of carboplatin by intraperitoneal injection is not recommended yet.Objective:HPLC method was established for the detection of carboplatin to study the pharmacokinetic difference of carboplatin through intraperitoneal injection and intravenous injection in order to explore the dosage of drug administration of carboplatin through intraperitoneal injection,and provide experimental basis for clinical hyperthermic intraperitoneal chemotherapy.Methods:1.HPLC method was established for the detection of carboplatin in perfusion fluid and plasma concentration,and the stability of carboplatin in peritoneal perfusion(normal saline)was investigated.2.An animal model with ascites caused by ovarian cancer was established,and the pharmacokinetic difference of carboplatin through intraperitoneal injection and intravenous injection was studied in order to explore the dosage of drug administration of carboplatin through intraperitoneal injection.3.The concentrations of carboplatin in ascites and plasma from patients with advanced ovarian cancer were determined,and the hematology indexes between two groups were compared before and after chemotherapy.Results:1.The blood samples were treated with 5-bromouracil as the internal standard and methanol as the precipitating agent.The flow phase was set to 97%water-3%methanol,which was suitable for the determination of carboplatin concentration in plasma.DAS2.0software was used to treat the blood drug concentration data after intravenous and intraperitoneal injection of 20mg/kg and 40mg/kg respectively.There were significant differences in the area between the two types of drug delivery(the vein was about 2~3times of the abdominal cavity).Carboplatin in 0.9%saline water as solvent,can keep stable within 24 h.2.Normal SD female rats were injected with Walker 256 cells in the abdominal cavity,and the ovarian cancer tumor model with ascites was successfully developed in 14days.Carboplatin was treated with intraperitoneal injection for the treatment of ovarian cancer:the peritoneal concentration of carboplatin was significantly higher than that of the blood concentration,and the effect of intraperitoneal ovarian cancer was better than that of intravenous injection.The blood toxicity of carboplatin was decreased by intraperitoneal injection than by blood injection.When the intraperitoneal injection dose was40mg/kg~80mg/kg,the increment of abdominal perimeter was the smallest after 7 days.3.When carboplatin was treated with intraperitoneal injection for the treatment of ovarian cancer,carboplatin was 2 to 4 times the concentration of plasma in the ascites,and the AUC of carboplatin in ascites was 2-3 times than that in plasma.There was no significant difference in blood toxicity index(the platelet count and the white blood count)between intravenous drip and HIPEC.Due to the small number of patients,it is necessary to further study whether there is a significant difference in blood toxicity caused by the two methods of administration.Conclusion:According to the results above,the conclusions are as follows:(1)Carboplatin in artificial ascites(0.9%saline for solvent)can be used in the abdominal cavity perfusion chemotherapy.(2)By the outcome of animal investigation,the dosage of carboplatin to adults treated by intraperitoneal injection was preliminarily determined to be245~491mg/m~2. |
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