[Pharmacokinetic study of intraperitoneal chemotherapy with high-dose cisplatin for advanced ovarian cancer].

OBJECTIVE

To determine the characteristics of pharmacokinetics with high-dose cisplatin (DDP) instilled intraperitoneally and its toxicity as compared with that by intravenous (i.v.) route of administration (i.p.).

METHODS

Sixteen patients with advanced ovarian cancer, not previously treated, were randomly divided into two groups: every patient in group I received intraperitoneal administration of DDP (100mg/m2) and those in group II received the same dose of DDP by intravenous route. The blood, ascitic fluid and urine were collected in different intervals as scheduled for 8 days after administration of these drugs. The total platinum of all samples were measured by a flameless type of atomic absorption spectrometry.

RESULTS

The concentration of total platinum in the ascitic fluid was very high in i.p. group. The area under the concentration-time curve (AUC) for total platinum in ascitic fluid after i.p. therapy was 5 folds greater than that after i.v. therapy (P < 0.05). The total platinum concentration in serum after i.p. therapy was about the same as that after i.v. therapy. The half-life time for the elimination phase of total platinum from ascitic fluid and serum after i.p. administration was longer than that after i.v. administration. The toxicity of high-dose DDP given i.p. was not increased as compared with that given i.v..

CONCLUSIONS

This study indicates that high-dose DDP i.p. therapy offers some advantages in the treatment of ovarian cancer. The tumor tissues and peritoneal growths could be bathed in a high concentrations of DDP with a longer duration, so that the tumorcidal effect may be increased. The drug concentration in serum after i.p. therapy was as high as i.v. route. The toxicity of high-dose DDP i.p. therapy was not higher than that of i.v. therapy.