Degradable starch microspheres in cytostatic treatment of a liver carcinoma; experimental studies in rats with 5-fluorouracil, tauromustine, carmustine, doxorubicin and RSU-1069.
The degradable starch microspheres (DSM) used have a size of 45 microns and are dissolved by amylase in blood. After intraarterial administration of a mixture of DSM and cytostatic drugs the coinjected drugs remain for a longer time in the target tissue/tumor. A transient hypoxia occurs. Systemic exposure of drugs is decreased. Rats with a carcinoma implanted into the liver were given DSM and drugs via the hepatic artery. DSM did not significantly increase the incorporation of 5-fluorouracil (5-FU) into liver tumor RNA. The incorporation of 5-FU into intestinal and bone marrow RNA increased. DSM increased the antitumor effect of doxorubicin, tauromustine, carmustine and RSU-1069 (aziridine 2-nitroimidazole). Side effects, such as liver and gastric necroses and body weight loss, appeared in some rats. The toxic overspill to the stomach seemed to be reduced by giving the DSM in two parts, with all the cytotoxic drug in the first part. The effect on liver and tumor was not decreased by this procedure. DSM alone had no anti-tumor effect. DSM alone decreased liver UDP-glucuronic acid in tumor-free rats, given either by the hepatic artery or, in the double dose, by the portal vein. DSM alone did not increase liver NADPH-cytochrome c reductase activity or serum ASAT (aspartate-aminotransferase) or ALAT (alanine-aminotransferase), indicating that the DSM are inert to the liver, when infused into the tributary vessels.
Roos
G
G
Department of Pathology, Lund University, Sweden.
Christensson
P I
PI
el Hag
I A
IA
Jakobsson
B
B
Teder
H
H
Stenram
U
U
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002330:Carmustine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005472:Fluorouracil / Q000008:administration & dosage; D007261:Infusions, Intra-Arterial; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D008863:Microspheres; D008920:Misonidazole / Q000008:administration & dosage / Q000031:analogs & derivatives; D009336:Necrosis; D009607:Nitrosourea Compounds / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D013213:Starch / Q000008:administration & dosage; D013270:Stomach / Q000098:blood supply; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives
D009607:Nitrosourea Compounds; D013654:Taurine; C052991:1-(2-chloroethyl)-3-(2-(dimethylaminosulfonyl)ethyl)-1-nitrosourea; D004317:Doxorubicin; C041712:1-(2-nitro-1-imidazolyl)-3-aziridino-2-propanol; D008920:Misonidazole; D000255:Adenosine Triphosphate; D013213:Starch; D005472:Fluorouracil; D002330:Carmustine