Kurihara N, Kubota T, Hoshiya Y, Otani Y, Watanabe M, Kumai K, Kitajima M
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
J Surg Oncol. 1996 Feb;61(2):138-42. doi: 10.1002/(SICI)1096-9098(199602)61:2<138::AID-JSO9>3.0.CO;2-D.
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.
使用两种人胃癌异种移植瘤（SC-1-NU和MKN-45）以及一种人乳腺癌异种移植瘤（MX-1）在BALB/c裸鼠中连续传代生长，对顺二氯二氨铂（II）（DDP）进行了药效学分析。DDP以5、10或20mg/kg的总剂量腹腔内注射（i.p.），给药方案为q7d×3或（qd×5）×3。DDP也腹腔内注射给BALB/c+/?小鼠，其血浆用于通过原子吸收法测定总铂和游离铂。20mg/kg DDP的总剂量似乎是对MX-1和SC-1-NU有效的最大耐受剂量。当总给药剂量相等时，q7d×3和（qd×5）×3给药方案的抗肿瘤效果彼此相似。DDP对MKN-45的抗肿瘤活性取决于总给药剂量以及血浆中游离铂和总铂的曲线下面积。当每千克总共给予10或20mg DDP时，使用（qd×5）×3给药方案在体重和脾脏重量减轻方面副作用明显减少。这些结果表明，当采用每日给药方案时，DDP可用于获得与推注注射相同的抗肿瘤活性，但副作用减少。
