Antitumor activities of seventeen alkylating agents against human mammary carcinoma (MS-1) in nude mice.

Abstract

The antitumor activities of seventeen antitumor alkylating agents have been studied in the xenograft of human mammary carcinoma transplanted in nude mice (MX-I). The drugs employed in this study were; cyclophosphamide. ifosfamide. 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (CCN U). 1-(2-ehloroethyl)­ 3-(4-methylcyclohexyl)-I-nitrosourea (me-CCN U). 2-[3-(2-ehloroethyl)-3-nitrosoureido]-2-deoxy- D­ glucopyranose (chlorozotocin. or OCN U). 3{(4-amino-2-methyI-5-pyrimidinyl)methyl]-I-(2-ehloro­ ethyl}-I-nitrosourea hydrochloride (ACN U). 1-(2-chloroethyl)-3-(methyl a-o-glucopyranos-6-yl)-I­ nitrosourea (M CN U). 1-(2-chloroethyl)-3-(I3-D-glucopyranosyl)-I-nitrosourea(GA NU). 4-[bis(2­ chloroethyl)amino]-L-phenylalanine (L-PA M). chlorambucil. busulfan. Bis(3-methylsulfonyloxy­ propyl)amine p-toluenesulfonate (864-T). N. N'. N"-triethylenimino thiophosphoramide (thio-TEPA). carbazilquinone. dibromomannitol, procarbazine and 5-(3. 3-dimethyl-l-triazeno) imidazole-4­ carboxamide (OTIC). Cyclophosphamide. ifosfamide. chlorozotocin. ACNU. MCNU. GANU, 864-T. thio-TEPA. carbazilquinone and OTIC were administered intravenously through a tail vein, and the others were given intra peritoneally. Among these seventeen antitumor alkylating agents, the most active compounds (maximum rate of tumor regression : ~O%) 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.