[Pharmacokinetics of carboplatin after intraperitoneal administration and clinical effect in ovarian cancer]

The patients with ovarian cancer are apt to combine peritonitis carcinomatosa (PC). The effect of intraperitoneal (IP) administration of CDDP against peritonitis carcinomatosa was examined. Hydration was not necessary when CBDCA was injected, because nephrotoxicity of CBDCA was very low compared to CDDP. We studied pharmacokinetics of IP-CBCCA and its efficacy and safety. Four hundreds and fifty mg of CBDCA was dissolved in 1,000 ml of saline and administrated through the subcutaneously implanted Infuse-A-Port for 60 minutes. Complete response was 25%. The platinum concentration in the ascites (injected saline) decreased to 90.8 micrograms/ml at 2 hr after administration and to 3.8 micrograms/ml at 24 hrs, and 79.7 97.5% existed as free Pt. The concentration of serous Pt reached to 6.2 micrograms/ml at 15 min. and was kept at 6-8 micrograms/ml. and 52.4-92.7% existed as free Pt in serum. Pt was excreted to urine and reached to the peak concentration at 4 hr. Adverse effect was mainly myelotoxicity without renal toxicity and emesis. Leukocytopenia of grade 4 was 14.3%, thrombocytopenia was 25.0%. We tried IP administration to the outpatients. The doses were mainly 300 mg, but in some cases, it was escalated to 450 mg, Adverse effect of 300 mg was thrombocytopenia of grade 4 (4.8%). These results suggest that IP administration of CBDCA seemed to be a new method as locosystemic chemotherapy. We demonstrated new chemotherapeutic method to outpatients.