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 mum an d are dissolved by amylase in blood. After intraarterial administratio n of a mixture of DSM and cytostatic drugs the coinjected drugs remain for a longer time in the target tissue/tumor. A transient hypoxia occ urs. Systemic exposure of drugs is decreased. Rats with a carcinoma im planted into the liver were given DSM and drugs via the hepatic artery . DSM did not significantly increase the incorporation of 5-fluorourac il (5-FU) into liver tumor RNA. The incorporation of 5-FU into intesti nal and bone marrow RNA increased. DSM increased the antitumor effect of doxorubicin, tauromustine, carmustine and RSU-1069 (aziridine 2-nit roimidazole). Side effects, such as liver and gastric necroses and bod y weight loss, appeared in some rats. The toxic overspill to the stoma ch seemed to be reduced by giving the DSM in two parts, with all the c ytotoxic 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 ei ther by the hepatic artery or, in the double dose, by the portal vein. DSM alone did not increase liver NADPH-cytochrome c reductase activit y or serum ASAT (aspartate-aminotransferase) or ALAT (alanine-aminotra nsferase), indicating that the DSM are inert to the liver, when infuse d into the tributary vessels.