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.