Direct diffusion of cis-diamminedichloroplatinum(II) in intraperitoneal rat tumors after intraperitoneal chemotherapy: a comparison with systemic chemotherapy.
Chemotherapy i.p. is increasingly being tested as a treatment modality for cancer limited to the peritoneal cavity. We have developed a rat tumor model in which penetration and distribution of cis-diamminedichloroplatinum(II) into intraperitoneal tumors have been studied. The platinum concentration in intraperitoneal tumor nodules, measured by two techniques, flameless atomic absorption spectroscopy and proton-induced X-ray emission, was always higher after i.p. treatment than i.v. Further, platinum concentrations were higher at the periphery of the tumor after i.p. administration than after i.v., while platinum concentrations in the center of the tumor nodules were identical. No difference was detected in platinum concentrations in s.c. tumors nor in the total area under the curve (plasma) after i.p. and i.v. administration of cis-diamminedichloroplatinum(II), suggesting that the higher drug concentration measured in peritoneal tumors after i.p. administration is due to direct diffusion of the drug from the peritoneal cavity.
Los
G
G
The Netherlands Cancer Institute, Division of Experimental Chemotherapy, Amsterdam.
Mutsaers
P H
PH
van der Vijgh
W J
WJ
Baldew
G S
GS
de Graaf
P W
PW
McVie
J G
JG
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D004058:Diffusion; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002945:Cisplatin