Comparison of tumor growth inhibitory and toxic effects of a new fluorouracil--nitrosourea derivative (B-3839).
The toxic effect and anti-tumor activity of B-3839, a new molecular combination of pyrimidine antimetabolite 5-fluorouracil (5-FU) with the alkylating agent N-Chloroethyl-N-nitrosourea (BCNU), was compared to that of BCNU and 5-FU given alone and in physical combination. The tumor inhibitory effect of B-3839 was similar to that of BCNU given alone or combined with a low dose of 5-FU in the i.m. Walker tumor model. Furthermore, the bone marrow toxicity of BCNU was not significantly altered by either form of combination with 5-FU. The intestinal side effects, evaluated by measuring the decrease of marker enzyme (thymidine kinase, xanthine oxidase, alkaline phosphatase, sucrase, maltase) activities in isolated enterocytes, were dose-dependent and moderate. A significant, more than 30%, decrease occurred only if BCNU and 5-FU were given simultaneously or as B-3839. The molecular combination of the two drugs does not provide any additional advantage over their physical combination.
Prajda
N
N
National Institute of Oncology, Budapest, Hungary.
Kralovánszky
J
J
Somfai-Relle
S
S
Gál
F
F
Kerpel-Fronius
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002279:Carcinoma 256, Walker / Q000188:drug therapy*; D002330:Carmustine / Q000627:therapeutic use / Q000633:toxicity; D004064:Digestive System / Q000187:drug effects / Q000473:pathology*; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D008297:Male; D009607:Nitrosourea Compounds / Q000627:therapeutic use* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; C060633:B 3839; D005472:Fluorouracil; D002330:Carmustine