Antiproliferative activity of 2-[N, N-bis-(2-chloroethyl)-amino]-4-[2-sulfonato-ethylthio]-tetrah ydr o-2H-1 , 3,2-oxazaphosphorine-2-oxide cyclohexamine (ASTA Z 7557, INN mafosfamide) against human and murine tumor cells in vitro.

The ability of ASTA Z 7557 to inhibit colony formation in vitro by 6 human tumor cell lines and 3 methyl-cholanthrene-induced murine fibrosarcomas was compared to that of cyclophosphamide, 4-hydroperoxy-cyclophosphamide, BCNU, cisplatin, mitomycin C, doxorubicin, and 5-fluorouracil, as a function of dose, and duration of exposure. All drugs except cyclophosphamide were active in a dose and time dependent manner against all cell lines. ASTA Z 7557 and 4-hydroperoxy-cyclophosphamide at equimolar concentrations had similar antiproliferative activities. The stabilities of ASTA Z 7557 and 4-hydroperoxy-cyclophosphamide as measured by cytotoxic activity remaining after incubation at various times at 37 degrees in complete tissue culture medium containing 10% fetal calf serum were identical. At initial concentrations of 20 microM, cytotoxic activity of both compounds began to decline after two hours of incubation and all activity was lost after 24 hours of incubation. In vitro, ASTA Z 7557 produced, at least, additive cytotoxic activity with cisplatin, the combination of cisplatin plus doxorubicin, and human lymphoblastoid interferon.