Antitumour activity of cis-diamminedichloroplatinum (II) against human tumour xenografts depends on its area under the curve in nude mice.
A pharmacodynamic analysis of cis-diamminedichloroplatinum(II) (DDP) was conducted using two human gastric cancer xenografts, SC-1-NU and MKN-45, and one human breast cancer xenograft, MX-1, grown serially in BALB/c nu/nu mice. DDP was administered intraperitoneally (i.p.) at a total dose of 5, 10, or 20 mg/kg in a schedule of q7d x 3 or (qd x 5) x 3. DDP was also administered i.p. to BALB/c +/? mice, whose plasma was used for the assay of total and free platinum by the atomic absorption method. A total dose of 20 mg/kg DDP seemed to be the maximum tolerated dose that was effective on MX-1 and SC-1-NU. When the totally administered doses were equivalent, the antitumor effects of the q7d x 3 and (qd x 5) x 3 schedules were similar to each other. The antitumor activity of DDP against MKN-45 was dependent on the total administered dose as well as the area under the curve of free and total platinum in the plasma. Side effects were significantly reduced using a schedule of (qd x 5) x 3 in terms of body and spleen weight loss when a total of 10 or 20 mg of DDP per kg was administered. These results suggest that DDP would be useful when administered using a daily schedule for obtaining the same antitumor activity as that of bolus injection but with reduced adverse effects.
Kurihara
N
N
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Kubota
T
T
Hoshiya
Y
Y
Otani
Y
Y
Watanabe
M
M
Kumai
K
K
Kitajima
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D004334:Drug Administration Schedule; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002945:Cisplatin