1980 Volume 71 Issue 2 Pages 157-170
The first clinical observation on intra-arterial infusion of microencapsulated anticancer drug (MMC-m. c.) is presented. The MMC-m. c., ethylcellulose microcapsules of mitomycin C (MMC), were prepared by us to be applied for intra-arterial infusion chemotherapy and proved to provide a sustained release property in vitro as well as in vivo. Thirty cases of kidney cancer were treated by transcatheter arterial embolization. The patients were classified into 3 treated groups; A) simple mechanical embolization using Gelfoam in 4 cases, B) chemoembolization using Gelfoam and MMC of usual dosage form in 10 cases and C) chemoembolization using Gelfoam and MMC-m. c. in 16 cases. Antitumor effects on tumor reduction measured by echography, angiography or CT scan, angiographic findings and histological changes were analized in the 3 treated groups. In groups B and C, bioavailability of MMC in the systemic blood and hematological toxicity were compared.
Tumor size was reduced by 30% or more in 7 cases of group C, comprising 13 cases, but tumor reduction was less than 30% in other cases including 6 cases of group C and 10 cases of group B. Repeated angiography in 6 cases of group B and 5 cases of group C showed that recanalization of tumor vessels was marked in 4 cases of group B, moderate in 2 of group B and 1 of group C, and slight in 2 of group C, but 2 cases of group C did not show recanalization for the observed period up to 4 months. Histological effect on tumor tissues obtained from 4 cases in group A, 5 in group B and 12 in group C was expressed by the extent of necrotic area. The effect was moderate in 2 cases and slight in 2 of group A, moderate in 3 and slight in 2 of group B, and marked in 8 and moderate in 4 of group C.
Systemic bioavailability of MMC in group C was 39% as compared with that of group B, suggesting a reduction of systemic toxicity by MMC in group C. Leukopenia occurred in 50%, erythropenia in 90% and thrombocytopenia in 80% of the cases in group B. On the other hand, the occurrence in group C were 0%, 60% and 55%, respectively.
The enhanced antitumor effects and reduced hematological toxicity in group C could be attributed to both the sustained release property of the MMC-m. c. and the microembolization of tumor vessels with the intra-arterial MMC-m. c.. Although our preliminary experience of chemoembolization with the microencapsulated anticancer drug is most encouraging, no effect on survival of disseminated cancer patients has yet been obtained from this mode of topical treatment. Further improvements of microencapsulation and controlled distribution of the microcapsules into metastatic lesions may overcome this problem.
