Antitumor activity of hexamethylmelamine on human tumor xenografts serially transplanted in nude mice.
The antitumor activity of hexamethylmelamine (HMM) was evaluated using four human tumor xenografts serially transplanted in nude mice. HMM was dissolved in 0.2 ml of 1% hydroxypropyl cellulose per mouse and administered perorally daily, except on Sunday, for 4 weeks, giving an estimated maximum tolerated dose (MTD) of HMM of 75 mg/kg. The MX-1 cell line showed dose-dependent sensitivity to HMM and was completely eradicated by treatment at the MTD. The minimum effective dose of HMM against MX-1 was calculated to be 22.1 mg HMM/kg, resulting in the chemotherapeutic index of 3.4. The demethylated derivatives of HMM, pentamethylmelamine and tetramethylmelamine, were also effective against MX-1, whereas trimethylmelamine was ineffective. The effect of HMM was more marked when the drug was administered on day 1 after tumor inoculation, compared with administration during the exponential growth phase. HMM is thought to be a promising agent for the treatment of several types of human carcinoma, producing active metabolites in vivo after peroral administration.
Kubota
T
T
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Tanino
H
H
Watanabe
M
M
Kitajima
M
M
D006585:Altretamine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D002277:Carcinoma / Q000188:drug therapy*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D013274:Stomach Neoplasms / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; C092289:N(2),N(2),N(4)-trimethylmelamine; C031537:N(2),N(2),N(4),N(6)-tetramethylmelamine; D006585:Altretamine; C022048:pentamethylmelamine