Berek J S, Schink J C, Knox R M
Department of Obstetrics and Gynecology, University of California, Los Angeles School of Medicine, Jonsson Comprehensive Cancer Center.
Obstet Gynecol. 1989 Oct;74(4):663-6.
The chemotherapeutic combination of cisplatin and cytosine arabinoside has synergy in vitro. We used a murine ovarian teratocarcinoma in C3HeB/FeJ mice to evaluate these drugs for synergy in vivo. Several dose-response schedules and various sequences were tested to determine the optimal delivery schedule. Survival of control mice injected with 10(4) murine ovarian teratocarcinoma was 28 days. Tumor-bearing mice treated with intraperitoneal cisplatin alone had significantly prolonged survival, whereas intraperitoneal cytosine arabinoside alone did not prolong survival. Repeated doses of cytosine arabinoside every 24 hours for 4 days resulted in minimal prolongation of survival. Simultaneous one-time administration of cisplatin and cytosine arabinoside resulted in synergy as measured by survival, with 50% of mice surviving at 80 days. Combined simultaneous administration of cisplatin and cytosine arabinoside daily for 3 days resulted in 100% survival at 120 days. Both cisplatin and cytosine arabinoside have an outstanding pharmacokinetic advantage when given intraperitoneally. A clinical trial of these drugs with a 3-day schedule is warranted.
顺铂和阿糖胞苷的化疗组合在体外具有协同作用。我们使用C3HeB/FeJ小鼠的鼠卵巢畸胎瘤来评估这些药物在体内的协同作用。测试了几种剂量反应方案和不同的给药顺序，以确定最佳给药方案。注射10⁴个鼠卵巢畸胎瘤的对照小鼠的生存期为28天。单独腹腔注射顺铂治疗的荷瘤小鼠生存期显著延长，而单独腹腔注射阿糖胞苷则未延长生存期。每24小时重复给药阿糖胞苷4天，生存期延长极少。顺铂和阿糖胞苷同时一次性给药，以生存期衡量显示出协同作用，50%的小鼠在80天时存活。顺铂和阿糖胞苷每日联合同时给药3天，120天时生存率达100%。顺铂和阿糖胞苷腹腔给药时均具有显著的药代动力学优势。对这些药物进行3天给药方案的临床试验是有必要的。
