Antitumor activity of menogaril alone, and in combination against human mammary cancer models in mice and rats.
Menogaril is an antitumor agent different from other anthracyclines in being active after oral administration. To predict its clinical effectiveness by this route against human breast cancer, we compared its antitumor activity against breast cancer in experimental animals with that of injected Adriamycin. Menogaril had half the much antitumor activity of Adriamycin against human mammary cancer cell lines. Menogaril given orally also had a antitumor activity against mammary cancer caused by 7,12-dimethyl-benz[a]anthracene in rats comparable with that of Adriamycin. The high concentration of menogaril in tumor tissue seemed to contribute to its effectiveness. Of several combinations of cyclophosphamide, Adriamycin, menogaril, and 5-fluorouracil, the combination of cyclophosphamide, menogaril, and 5-fluorouracil was most effective against mouse leukemia L1210 and human breast cancer xenografts in mice. This combination might have antitumor activity against breast cancer superior to that of the therapy currently of first choice (cyclophosphamide, Adriamycin, and 5-fluorouracil) in the clinic.
Yoshida
M
M
Anticancer and Antimicrobials Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Fujioka
A
A
Nakano
K
K
Kobunai
T
T
Saito
H
H
Toko
T
T
Takeda
S
S
Unemi
N
N
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002273:Carcinogens; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D017290:Menogaril / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D013936:Thymidine / Q000378:metabolism; D014183:Transplantation, Heterologous; D014316:Tritium; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D002273:Carcinogens; D014316:Tritium; D015127:9,10-Dimethyl-1,2-benzanthracene; D004317:Doxorubicin; D017290:Menogaril; D003520:Cyclophosphamide; D005472:Fluorouracil; D013936:Thymidine