Synergistic effect of combined intraperitoneal cisplatin and cytosine arabinoside in a murine ovarian cancer model.
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.
Berek
J S
JS
Department of Obstetrics and Gynecology, University of California, Los Angeles School of Medicine, Jonsson Comprehensive Cancer Center.
Schink
J C
JC
Knox
R M
RM
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005260:Female; D051379:Mice; D008809:Mice, Inbred C3H; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D013724:Teratoma / Q000188:drug therapy*
D003561:Cytarabine; D002945:Cisplatin