Experimental and clinical studies on the intraperitoneal administration of cis-diamminedichloroplatinum (II) for peritoneal carcinomatosis caused by gastric cancers.
The effectiveness of the intraperitoneal administration of cis-diamminedichloroplatinum (II) (DDP) on peritoneal carcinomatosis caused by gastric cancers was evaluated. Seventeen patients were treated with one of three protocols, consisting of the intraperitoneal injection (ip) of DDP at doses of 70 and 110 mg/m2, with or without sodium thiosulfate (STS) rescue. The area under the curve (AUC) of DDP for sufficient anticancer activities against cultured human cell lines in vitro was estimated at 240 micrograms h/ml, which was equivalent to the AUC gained by 110 mg/m2 ip DDP in the clinical studies. The cytotoxic activity of DDP was reduced by approximately 50% with 100-fold STS in the AUC in the experimental studies. However, this was achieved only in urine, and not in either the peritoneal cavity or in plasma in the clinical studies. Three cases of a partial response against peritoneal carcinomatosis were seen from a total of four evaluable cases treated with 110 mg/m2 DDP, and no renal toxicities were observed in those treated with the STS rescue. The results of this study led us to conclude that high-dose ip DDP treatment combined with the STS rescue would be useful chemotherapy against peritoneal carcinomatosis caused by gastric cancers.
Furukawa
T
T
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Kumai
K
K
Kubota
T
T
Hirahata
S
S
Shimizu
H
H
Matsui
H
H
Takahara
T
T
Aizawa
K
K
Shibata
S
S
Shimada
A
A
D000328:Adult; D000368:Aged; D000931:Antidotes / Q000008:administration & dosage / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002461:Cell Line, Transformed; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics; D003470:Culture Media; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D008297:Male; D008875:Middle Aged; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D013274:Stomach Neoplasms / Q000473:pathology*; D013885:Thiosulfates / Q000008:administration & dosage / Q000493:pharmacokinetics
D000931:Antidotes; D003470:Culture Media; D013885:Thiosulfates; C017717:sodium thiosulfate; D002945:Cisplatin