Shimizu Y, Fujiwara A, Akagaki E, Hirota K, Kono M, Irie T, Miura S, Okudaira Y
Gan To Kagaku Ryoho. 1986 May;13(5):1934-9.
Consecutive intraarterial infusion of cis-diamminedichloroplatinum (CDDP) with continuous intraarterial infusion of 5-fluorouracil (5-FU) (250 mg/day) was administered to 10 patients with locally advanced (peritonitis carcinomatosa) ovarian cancer. The dose of CDDP was 10 mg/5 min/body/day and it was administered for about 10-20 consecutive days per one course. Each course was repeated at about 3-week intervals. The main dose-limiting factor was the number of peripheral leucocytes. The results were 6 PR, 1 MR and 2 NC out of 9 evaluable cases, all of whom had had previous therapy. The antitumor effect needed over 200 mg of intraarterial CDDP and the response lasted from 2 to more than 9 months. Among 6 patients who obtained PR, 4 had failed to respond to intravenous or intraperitoneal infusion of CDDP, which suggested that a high concentration and a critical drug gradient across the tumor cell membrane were more essential for a significant tumor cell kill, with CDDP, than the time of exposure. The toxic effects of intraarterial infusion of CDDP were almost absent as compared with those of intravenous infusion, which consisted of nausea and vomiting. Renal dysfunction was also mild. Other toxic effects were not different from those observed in intravenous infusion. Our results with intraarterial infusion of CDDP clearly indicate that this approach can deliver a high therapeutic efficacy in patients with advanced ovarian cancer with markedly less toxic effects.
对10例局部晚期(癌性腹膜炎)卵巢癌患者连续进行顺二氯二氨铂(CDDP)动脉内输注,并持续动脉内输注5-氟尿嘧啶(5-FU,250毫克/天)。CDDP的剂量为10毫克/5分钟/体/天,每疗程连续给药约10至20天。每个疗程间隔约3周重复进行。主要剂量限制因素是外周血白细胞数量。9例可评估病例中,结果为6例部分缓解(PR)、1例病情稳定(MR)和2例疾病无进展(NC),所有患者均曾接受过先前治疗。抗肿瘤效果需要动脉内输注超过200毫克的CDDP,缓解持续时间为2至9个月以上。在6例获得PR的患者中,有4例对CDDP静脉或腹腔内输注无反应,这表明与暴露时间相比,高浓度和顺铂跨肿瘤细胞膜的临界药物梯度对于显著杀伤肿瘤细胞更为重要。与静脉输注相比,动脉内输注CDDP的毒性作用几乎不存在,静脉输注的毒性作用包括恶心和呕吐。肾功能障碍也较轻。其他毒性作用与静脉输注观察到的情况无异。我们动脉内输注CDDP的结果清楚地表明,这种方法可以在晚期卵巢癌患者中产生高治疗效果,且毒性作用明显较小。