Antitumor Activities of Seventeen Alkylating Agents Against Human Mammary Carcinoma (MX-1) in Nude Mice

The antitumor activities of seventeen antitumor alkylating agents have been studied in the xenograft of human mammary carcinoma transplanted in nude mice (MX-1). The drugs employed in this study were; cyclophosphamide, ifosfamide, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), 1-(2-chloroethyl)- 3-(4-methylcyclohexyl)-1-nitrosourea (me-CCNU), 2-3-(2-chloroethyl)-3-nitrosoureido-2-deoxy- D-glucopyranose (chlorozotocin, or DCNU), 3(4-amino-2-methyl-5-pyrimidinyl)methyl-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU), 1-(2-chloroethyl)-3-(methyl α-D-glucopyranos-6-yl)-1-nitrosourea (MCNU), 1-(2-chloroethyl)-3-(β-D-glucopyranosyl)-1-nitrosourea(GANU), 4-bis(2- chloroethyl)amino-L-phenylalanine (L-PAM), chlorambucil, busulfan, Bis(3-methylsulfonyloxypropyl)amine p-toluenesulfonate (864-T), N, N', N"-triethylenimino thiophosphoramide (thio-TEPA), carbazilquinone, dibromomannitol, procarbazine and 5-(3, 3-dimethyl-1-triazeno) imidazole-4- carboxamide (DTIC). Cyclophosphamide, ifosfamide, chlorozotocin, ACNU, MCNU, GANU, 864-T, thio-TEPA, carbazilquinone and DTIC were administered intravenously through a tail vein, and the others were given intraperitoneally. Among these seventeen antitumor alkylating agents, the most active compounds (maximum rate of tumor regression : ≧9O%) are cyclophosphamide, ACNU, L-PAM, chlorambucil, thio-TEPA, carbazilquinone and dibromomannitol. Another group of compounds showed moderate activity (maximum rate of tumor regression: 89-50%), including ifosfamide, CCNU, MCNU, GANU, busulfan, 864-T and procarbazine. The remaining three compounds showed less than moderate activity (≦49%) and were therefore considered to be inactive. These results in nude mouse-human tumor xenograft system correspond to clinically observed patterns of chemotherapy sensitivity in patients with breast cancer.