IN-VIVO ANTITUMOR-ACTIVITY OF HEXAMETHYLMELAMINE AGAINST HUMAN BREAST, STOMACH AND COLON-CARCINOMA XENOGRAFTS

We have evaluated the antitumor activity of Altretamine (hexamethylmel amine, HMM) on human carcinoma xenografts serially transplanted in nud e mice. Five human breast carcinoma xenografts, MX-1, T-61, MCF-7, R-2 7 and Br-10, were inoculated subcutaneously into female nude mice. Two human stomach carcinoma xenografts, SC-1-NU and St-4, and three human colon carcinoma xenografts, Co-3, Co-4 and Co-6, were inoculated subc utaneously into male nude mice. One pellet of 17 beta-estradiol (0.1 m g/mouse) was inoculated subcutaneously in the mice transplanted with M CF-7 when the tumors were inoculated. HMM was administered per os dail y for 4 weeks. MX-1 and T-61 tumors regressed completely after treatme nt with HMM at a dose of 75 mg/kg (the maximum tolerated dose: MTD) fo r MX-1 and 25 mg/kg for T-61. Br-10 was sensitive, whereas MCF-7 and R -27 were resistant to HMM at its MTD. HMM exerted the most potent anti tumor effect against T-61. Against MX-1, it exerted an antitumor effec t equivalent to that of cisplatin or cyclophosphamide. In addition, th is agent was effective against all stomach and colon carcinoma xenogra fts, in particular St-4 (T/C% = 10.7: the mean tumor weight of treated group/the mean tumor weight of control group) and Co-3 (T/C% = 31.5%) which are insensitive to presently available agents. HMM seems worthy of further clinical investigation as a candidate agent to treat breas t, stomach, colon and other carcinomas.