[A new anticancer preparation, 5-fluorouracil-poly-L-lactic acid microcapsule, and its therapeutic evaluation]

An attempt was made to develop the new anticancer drug inducing enhanced tumor response to arterial chemoembolization therapy. 5-Fluorouracil (5-FU) was microencapsulated with poly L-lactic acid by the organic phase separation technique. This granular preparation containing 5-FU (FU-PLA-mc) was about 200 micron in diameter and was about 40% in 5-FU content. The release of 5-FU in vitro from FU-PLA-mc gradually increased, extending over 50 hours to reach maximum level. When 75 mg of FU-PLA-mc (5-FU content, 30 mg) was infused into normal rabbits through femoral arteries, maximum level of 5-FU in blood was 1.03 +/- 0.16 microgram/g after 15 minutes. Meanwhile, arterial infusion of the same dosage of FU-PLA-mc into VX2 tumor bearing rabbits resulted in the production of high level of 5-FU (2.1 +/- 0.5 micrograms/g) in tumors even after 72 hours. In vivo anticancer effect of FU-PLA-mc was significantly demonstrated; when 75 mg of FU-PLA-mc was administrated to VX2 tumor bearing rabbits through arterial infusion, T/C ratio of mean tumor weight was 0.01% on the 14th day after infusion. After hepatic arterial embolization with FU-PLA-mc in normal rabbits, elevation of serum transaminases was observed, but it was transient. Hepatic arterial chemoembolization with FU-PLA-mc was carried out for 8 patients with hepatic malignancies. Of these 8 patients, partial response was obtained in 3 patients and no severe complication was observed.