The use of oxaliplatin versus cisplatin in intraperitoneal chemotherapy in cancers restricted to the peritoneal cavity in the rat.
Pharmacokinetic studies demonstrated the advantage of intraperitoneal oxaliplatin (1-OHP) for cancers restricted to the peritoneal cavity. The area under the concentration X time curve (AUC) in the peritoneal cavity for both total and ultrafiltered drug was almost 2 times higher for 1-OHP than cisplatin (cDDP). The AUC for ultrafiltered 1-OHP in plasma was also a factor 4 higher than cDDP, indicating that peritoneal tumors received a higher exposure from 1-OHP than cDDP directly in the peritoneal cavity and indirectly via the systemic circulation. Total platinum concentrations in peritoneal tumors of rats were determined after i.p. administration of equimolar doses of 1-OHP and cDDP. In spite of the pharmacological advantages, no significant difference in platinum concentration was demonstrated. In addition, no difference in the distribution of platinum within peritoneal tumors was detected after i.p. treatment with equimolar doses, i.e., platinum concentrations were comparable both in the periphery, 29 +/- 4 ppm for cDDP and 22 +/- 8 for 1-OHP and in the center of the tumor, 18 +/- 3 for both drugs. When CC531 tumor cells were incubated in vitro with equimolar concentrations of 1-DHP and cDDP in vitro, 2 to 4 times less platinum was found in cells treated with 1-OHP, indicating that the uptake of 1-OHP differed from that of cDDP. Oxaliplatin was not cross resistant for cDDP in CC531.RL4 tumor cells, a cDDP resistant cell line, which may indicate its value in ovarian cancer patients who did not respond to earlier cDDP treatment.
Los
G
G
The Netherlands Cancer Institute, Division of Experimental Therapy, Amsterdam.
Mutsaers
P H
PH
Ruevekamp
M
M
McVie
J G
JG
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001202:Ascitic Fluid / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003110:Colonic Neoplasms / Q000032:analysis / Q000473:pathology; D007274:Injections, Intraperitoneal; D008297:Male; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077150:Oxaliplatin; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D051381:Rats; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002945:Cisplatin