Antitumor activity of cis-diamminedichloroplatinum II against human tumor xenografts depends on its area under the curve in nude mice

✍ Scribed by Kurihara, Naoto; Kubota, Tetsuro; Hoshiya, Yasunori; Otani, Yoshihide; Watanabe, Masahiko; Kumai, Koichiro; Kitajima, Masaki

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 466 KB
• Volume: 61
• Category: Article
• ISSN: 0022-4790
• DOI: 10.1002/(sici)1096-9098(199602)61:2<138::aid-jso9>3.0.co;2-d

✦ Synopsis

A pharmacodynamic analysis of cis-diamminedichloroplatinum(I1) (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 intrapentoneally (ip) at a total dose of 5, 10, or 20 mgkg in a schedule of q7d X 3 or (qd X 5) X 3. DDP was also administered ip 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 mgkg 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.