Intra-arterial infusion of doxorubicin with degradable starch microspheres. Improvement of hepatic tumor drug uptake
E. R. Sigurdson, J. A. Ridge and J. M. Daly
Regional infusion chemotherapy delivers higher drug concentrations to the
tumor than other methods and may decrease systemic drug levels. We
evaluated the efficacy of degradable starch microspheres (DSMs) to further
increase drug delivery to hepatic tumors. Rabbits implanted with hepatic
Vx-2 tumors were treated with hepatic arterial infusion of doxorubicin
hydrochloride labeled with carbon 14 with and without DSMs. Tissue levels
of doxorubicin were measured in the heart, liver, and tumor 30 minutes
after drug infusion. Blood drug levels, as well as biliary and renal
excretion rates of doxorubicin, were determined. In rabbits receiving the
drug alone, doxorubicin uptake by the tumor and liver were 17.1 +/- 12.8
and 55.3 +/- 9.5 nmol/g of wet weight tissue (mean +/- SD), respectively.
In rabbits receiving doxorubicin mixed with DSMs, the tumor and hepatic
drug levels were 59.7 +/- 24.9 and 50.7 +/- 4.8 nmol/g, respectively. The
tumor drug level was significantly higher in the group that received DSMs
compared with the group that received only the drug; the hepatic drug
uptake was unchanged. Peak blood and cardiac drug levels were decreased by
the coinfusion of drug and DSMs, suggesting that tumor response rates may
be improved and systemic toxicity diminished by the use of DSMs in regional
infusion chemotherapy.
