Cisplatin combined with prostaglandin E1 chemotherapy in rat peritoneal carcinomatosis.
Cisplatin intraperitoneal (i.p.) chemotherapy is frequently performed for patients with peritoneal carcinomatosis. However, cisplatin penetrates only the surface of the peritoneal tumor and has serious side effects on renal cells. Thus, cisplatin i.p. chemotherapy had been limited to use for these patients. Prostaglandin E1 (PGE1) has been used for reducing the toxic effects of anticancer drugs because of its cytoprotective effects and has been reported to enhance tumoricidal activity of anticancer drugs. In our study, the effects of PGE1 on the rat peritoneal carcinomatosis model treated with cisplatin i.p. chemotherapy were evaluated. Cisplatin (5 mg/kg) was given in an i.p. administration to 70 tumor-free rats. PGE1 was administered to 35 rats through the tail vein at an infusion rate of 0.1 microg/kg/min (1 ml/hr), and the remaining 35 rats were injected with physiological saline. Forty rats were given an i.p. injection of 1 x 10(7) AH100B cells. Ten days after injection, cisplatin (5 mg/kg) was administered with PGE1 to 20 and the remaining 20 were injected with physiological saline. The accumulation of platinum in the tissues and apoptotic renal cells were analyzed. The maximum concentrations of platinum in the kidneys of PGE1 untreated rats (tumor-free: 10.11 microg/g; tumor-bearing: 11.45 microg/g) did not differ from those of platinum in the kidneys of PGE1-treated rats (tumor-free: 10.28 microg/g; tumor-bearing: 13.28 microg/g). The number of apoptotic renal cells was significantly reduced by PGE1 administration in both tumor-free and tumor-bearing rats. Moreover, PGE1 increased the maximum platinum concentration in tumor masses (5.31 microg/g) of the treated group compared with that in tumor mass of the control group (2.72 microg/g, p = 0.009). These results indicate that PGE1 may increase the anticancer effect of cisplatin by increasing tumor platinum concentration and may reduce the chance of cisplatin-induced renal failure. Intraperitoneal cisplatin chemotherapy combined with PGE1 treatment may have a therapeutic benefit for patients with peritoneal carcinomatosis.
Ikeguchi
M
M
Department of Surgery I, Faculty of Medicine, Tottori University, Yonago, Japan.
Maeta
M
M
Kaibara
N
N
D000527:Alprostadil / Q000008:administration & dosage*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D019610:Cytoprotection; D004359:Drug Therapy, Combination; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010984:Platinum / Q000493:pharmacokinetics; D051381:Rats
D000970:Antineoplastic Agents; D010984:Platinum; D000527:Alprostadil; D002945:Cisplatin