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.