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Obstetrics & Gynecology 1989;74:663-666
© 1989 by The American College of Obstetricians and Gynecologists
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Synergistic Effect of Combined Intraperitoneal Cisplatin and Cytosine Arabinoside in a Murine Ovarian Cancer Model

JONATHAN S. BEREK, MD, JULIAN C. SCHINK, MD and AND REBA M. KNOX, MS

From the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of California, Los Angeles School of Medicine, Jonsson Comprehensive Cancer Center, Los Angeles, California.

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 104 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.






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Copyright © 1989 by the American College of Obstetricians and Gynecologists.