[Intraperitoneal administration of cis-diamminedichloroplatinum (II) for peritoneal carcinomatosis caused by gastric cancers].
The effectiveness of the intraperitoneal administration of cis-diamminedichloroplatinum (II) for peritoneal carcinomatosis by gastric cancers was evaluated through experimental and clinical studies. In experimental studies, the effect of sodium thiosulfate (STS) on cytotoxic activity of DDP was evaluated by MTT assay using human gastric cancer cell lines. The cytotoxic activity of DDP was reduced by 50% with 100-fold STS in the area under the curve (AUC), whereas 10-fold STS in AUC did not reduce the cytotoxicity of DDP. In clinical studies, patients were treated with one of three protocols: Group A was treated by the intraperitoneal injection (ip) of DDP at a dose of 70 mg/m2, and group B or C was treated by ip DDP at a dose of 110 mg/m2 with or without STS rescue. The pharmacodynamics and the adverse effects of treatments were evaluated between these three protocols. In group C, the means of AUC of STS were 2.43-, 10.8- and 86.8-fold those of total platinum in the peritoneal cavity, plasma, and urine, respectively. There were 1/5, 1/2 and 2/2 partial responses in peritoneal carcinomatosis patients treated with A, B and C. Renal toxicity was not observed in the patients treated with DDP and STS rescue. STS does not seem to reduce the antitumor activity of DDP in peritoneal cavity and plasma, while the renal cytotoxicity was reduced by STS rescue. The result led us to conclude that intraperitoneal DDP treatment combined with STS rescue would be useful chemotherapy against peritoneal carcinomatosis by gastric cancer.
Kurihara
N
N
Dept. of Surgery, School of Medicine, Keio University.
Kumai
K
K
Kubota
T
T
Furukawa
T
T
Yamamoto
T
T
Shimada
A
A
Shibata
S
S
Saikawa
Y
Y
Ogawa
S
S
Murayama
Y
Y
D000328:Adult; D000368:Aged; D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D010538:Peritonitis / Q000188:drug therapy* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000150:complications / Q000473:pathology*; D013885:Thiosulfates / Q000008:administration & dosage; D014407:Tumor Cells, Cultured
D013885:Thiosulfates; C017717:sodium thiosulfate; D002945:Cisplatin