[Pharmacokinetic analysis in intraperitoneal hyperthermic perfusion using mitomycin C in far-advanced gastric cancer].
Postoperative intraperitoneal hyperthermic perfusion (IPHP) using MMC was performed with marked success on 15 gastric cancer patients with peritoneal dissemination or serosal invasion (first surgery group) and on 5 recurrent gastric cancer patients with ascitic retention (recurrent cancer group), and the MMC concentrations was studied in the perfusate and circulating blood. The perfusate contained MMC 10 micrograms/ml at the onset of IPHP, except one recurrent case of 20 micrograms/ml, and IPHP was performed for 120 minutes except in one case given 20 micrograms/ml of MMC. There was little difference in the hepatorenal functions and perfusate temperatures between the first surgery group and the recurrent cancer group. The drug levels were measured by HPLC method with minimal assay levels of 2 ng/ml. Perfusate drug levels in the first surgery group reduced by half at 12 minutes after the start of IPHP, whereas in the recurrent cancer group, they decreased by half about 60 minutes later. Perfusate drug levels in the first surgery group decreased twice as rapidly as in the recurrent cancer group. The area under the curve (AUC) and average drug levels in the first surgery group were 7,900 micrograms.hr/l and 3.3 micrograms/ml, respectively, and those in the recurrent cancer group were 12,620 micrograms.hr/l and 5.3 micrograms/ml, respectively. On the other hand, the drug levels in peripheral blood were almost the same between the two groups. These data suggest that although recurrent gastric cancer is well suited for IPHP because of high AUC, it is worthwhile performing IPHP combined with surgery for gastric cancer with peritoneal seeding, with due consideration for AUC of 7,900 micrograms.hr/l and the average drug level of 3.3 micrograms/ml.
Fujimoto
S
S
First Dept. of Surgery, School of Medicine, Chiba University.
Shrestha
R D
RD
Kokubun
M
M
Kobayashi
K
K
Kiuchi
S
S
Ohta
M
M
Takahashi
M
M
Konno
C
C
Koike
S
S
Okui
K
K
D000328:Adult; D001202:Ascitic Fluid / Q000628:therapy; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D007263:Infusions, Parenteral; D008297:Male; D016685:Mitomycin; D008937:Mitomycins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*
D008937:Mitomycins; D016685:Mitomycin