BISDIOXOPIPERAZINE, (-1,2-BIS(3,5-DIOXOPIPERAZINYL-1-YL)PROPANE (ICRF-187), ENHANCES THE ANTIPROLIFERATIVE EFFECT OF CISPLATIN ON HUMAN OVARIAN-CANCER CELLS())

The bisdioxopiperazine ICRF 187 is a potent intracellular chelating ag ent which effectively diminishes Adriamycin cardiotoxicity without com promising its antitumor activity. Our study aimed at verifying whether ICRF 187 can modulate the cytotoxic action of cisplatin (CDDP) on ova rian cancer cells. We used the A2780 ovarian cancer cell line and a su bline resistant to CDDP (A2780-CDDP) obtained in our laboratory by con tinuous exposure of the parental cells to progressively increasing CDD P doses. In both cell lines ICRF 187 (0.1-0.5 mu g/ml) used in combina tion with CDDP (0.01-1 mu g/ml) produced a dose-dependent reduction of CDDP IC50 (the concentration inhibiting 50% of cell growth). Moreover , when ICRF 187 was used in combination with CDDP, analysis of the dat a by the isobole method showed that the combination of the two drugs p roduced a synergistic antiproliferative activity in both cell lines, w ith a CDDP potentiation up to fivefold. Our in vitro data show that IC RF 187 can synergize with CDDP. Prospective clinical trials are now ne eded to verify whether the addition of ICRF 187 to CDDP-containing reg imens will result in an improved clinical response in ovarian cancer. (C) 1995 Academic Press, Inc.