Clinical application of chemotherapy via the portal vein with liposome-encapsulated adriamycin in inoperable metastatic liver cancer

We studied the effects of liposome-entrapped adriamycin (L-ADM) administered via the portal vein and the clinical application of this treatment in the therapy and inhibition of liver metastasis, experimentally and clinically. Liposomes composed of egg phosphatidylcholine (cholesterol 50 mol%) were used as drug carriers. We examined the distribution in tissues and antitumor effect of freeze-dried L-ADM administered via the portal vein to rabbits bearing VX2 tumors. The liver concentration of ADM increased after delivery and cardiac uptake decreased compared with free drug treatment. The life span was prolonged by L-ADM treatment compared with the control group and the free ADM group. This L-ADM administration was confirmed to be safe and revealed a decrease in the heart toxicities compared with free adriamycin. Nineteen cases were studied from Jan. 1986 to May 1991 via the portal vein and the clinical effects were evaluated. From Mar. 1988 to date, 10 cases were treated with L-ADM (20-30 mg every 2 weeks/body) in patients with inoperable cases using subcutaneously implanted reservoir. The median survival was 450 days; 275 days for colon cancer, 492 days for gastric cancer, and 1,052 days for uterine cancer (range: 136-1,152 days), compared with 141 days (range: 52-253 days) in 9 cases of historical control treated with free-ADM via the portal vein. These results suggest that chemotherapy via the portal vein with L-ADM for metastatic liver cancer may increase survival time.