Hyperthermic Perfusion Chemotherapy Of Mitomycin C Pharmacokinetics And Clinical Efficacy And Safety Study

Part1Pharmacokinetic study of hyperthermic perfusionchemotherapy of mitomycin CObjectHigh performance liquid chromatography (HPLC) determination of the five enrolledpatients intravesical perfusion chemotherapy at different time points of blood andperfusion fluid concentration of MMC, the MMC concentration in the blood andperfusion fluid at different time points were observeddynamicallyintravesicalperfusion chemotherapy process at different time points MMCuptake, hyperthermic perfusion chemotherapy (HIVEC) pharmacokinetic studiesprovide the experimental basis.Method1. Indwelling experimental specimensPerfusion the equipartition different time point specimens of serum andperfusionfluid samples, using high performance liquid chromatographic assay ofblood andperfusion fluid samples MMC concentration.2. sample preparation methodExtract blood3~5mL dry test tube, placed insulation refrigerator3hours, andthencontrol the centrifuge4℃1500rev/min, centrifuged for10minutes, distributedinto200ul4were placed in-80℃refrigerator. Perfusion liquid specimen50ml drytest-tube specimens, distributed into4to5small test tube, and placed in-80° Crefrigerator.3. HPLC method for the detection ofTake the perfusion fluid and serum samples, After pretreatment, injection islandofbody fluid chromatography, high performance liquid chromatography(HPLC)detection of the sample peak area obtained plasma plus standardchromatogram of plasma chromatography Figure, the perfusion liquidchromatogram.The measured peak area and the drugs of different concentrations of thestandardcurve of peak area on behalf of into the regression equation calculate the thedrugdetermination of concentration, take a patient sample determinationofconcentration mean, draw the drug of the time-concentration change curve, theuse of DAS2.0software to calculate the pharmacokinetic parameters.Result1.0.5-50ng/ml for the linear range of the standard plasma concentration as theabscissa (x), the MMC peak area for the vertical axis (y) for linear regression, theresulting linear equation y=bx+a: y=0.0108±0.0001x+0.005±0.003, r=0.999.2. Take the determination of MMC in the plasma concentration mean time-concentration curves obtained draw the drug area under the concentration-timecurve (AUC) was187(167to468) ng/ml/min.3. Bladder perfusion chemotherapy blood samples0min,15min,30min,45min and60min determination of MMC concentration (mean±standard deviation) were:3.25±3.34ng/ml、4.57±3.82ng/ml、5.23±3.43ng/ml、7.65±6.24ng/mland7.57±5.30ng/ml.The peak plasma concentration of mitomycin45~60min,and reached a plateau.4. Bladder perfusion chemotherapy perfusion fluid samples from0min,15min,30min,45min determination of MMC concentration (mean±standard deviation)were:85±21ug/ml、73±18ug/ml、68±20ug/ml、65±16ug/ml. Conclusion1. HIVEC when plasma MMC concentrations were lower peak below the thresholdconcentration of400ng/ml of bone marrow suppression.2. bladder perfusion therapy intravesical MMC concentration higher MMCconcentration is not obvious change over time.Part2Clinical safety studies of the hyperthermicperfusion chemotherapy of mitomycin CObjectChanges in vital signs and adverse reactions in the process of observation intothegroup of patients with bladder perfusion chemotherapy, regular follow-up toobservethe clinical efficacy and toxicity of HIVEC provide research evidence,clinicaltreatment efficacy and safety.Method1.12cases of14patients in this group of male and2females, Karnofsky score of90to100. Multiple patients were TCC or recurrence of bladder cancer patients,confirmedby cystoscopic biopsy or surgical pathology of TCC, serious liver andkidney dysfunction and cardio-pulmonary disease, admission midfielder hardanesthesiatransurethral bladder tumor transurethral surgery. Patients with bladderperfusionchemotherapy three times a80mg MMC sterile saline to600ml,perfusiontemperature of45°C, perfusion time60min, the infusion rate150ml/min.2. Perfusion observed during the lives of patients with characteristic changesinperfusion after close review the changes in the patient’s blood count,electrolytes,liver and kidney functions, select the side effects of chemotherapy, thedigestive tractof anti-cancer drug developed by the WHO acute and subacute toxicityevaluation ofperformance and grading standardsfill chemotherapy observed table.Were followedup for6to24months, regular cystoscopic review of patients’tumors change in statuseffects were observed. Result1. Intravesical perfusion in patients with chemotherapy during the vital signs ofpatientsno obvious abnormalities, skin temperature was normal, no treatment-relatedserious adverse events. Four cases of patients with urinary frequency, urgency,dysuria,urinary discomfort and symptoms gradually disappeared3days to2weeksafter treatment. Gastrointestinal side effects0~I order reaction, with no nausea,vomiting and other gastrointestinal reactions.④All patients the day afterreperfusion, blood routine, electrolytes, liver and kidney function, blood sampleshowed no obvious abnormalities, no case of bone marrow suppression, liver andkidney dysfunction.2. Cystoscopy after3months after treatment, showed a normal bladder mucosa, nosignificant congestion, edema, scarring, bilateral ureter, normal spray urine,takenormal bladder mucosa appearance, see no abnormal urethra, nourethralhyperemia, edema, urethral stricture. The pathology results showed that: aclear structure of the bladder mucosa, glands arranged in neat rows, no obviousabnormalities. Review B,no kidney, the occurrence of hydroureter.3. All14patients were followed up for up for12to24months, with an average of20months. Patients were alive without pelvic lymph node metastasis and distantmetastasis. Three cases of bladder local recurrence, the recurrence time for6to12months, an average of10months with a median time of18months, recurrence of thenumber of1to2, with an average of1.7, patients with recurrence aftertransurethralbladder tumor transurethral resection. One patient relapse, afterDecember HIVECtreatment, the the TURBT postoperative re HIVEC treatmentcourse of treatment,follow-up in December not to see the recurrence; the other twocases of recurrence in patients with TURBT after surgery did not undergo thistreatment, local tumor again inJune recurrence; I patients had no recurrence.Conclusion1. Bladder perfusion chemotherapy used in the clinical safety and reliable.2. In the treatment program, HIVEC treatment of human vital signs without obviousadverse effects, no serious adverse events.3. The bladder HIVEC of the high risk of recurrence of superficial TCCpatients,mitomycin line treatment allows tumor recurrence time, and recurrencereduction in the number and reduce the relapse rate of patients STCCB.