Chemoembolization in liver malignant involvement. Experiences on 17 cases

Liver invasion is the major cause of organ failure in patients with primary liver cancer and metastatic large bowel cancer. Furthermore it causes high morbidity in many other carcinomas. The normal liver presents a double circulation: 75% from portal circulation and 25% from hepatic artery. In malignant primary and secondary lesions the blood support is given by hepatic artery. Antineoplastic drugs mixed to selectively injecting embolic particles, such as polyvinyl alcohol and gelatin powder (Gelfoam), can be injected to infarct tumors and to obtain a therapeutical advantage. Chemoembolization using an emulsion of Lipiodol ultra-fluid (LUF) and drugs is a recent tool in liver regional therapy. LUF has been shown to be taken up hepatocellular carcinoma and retained for a long period of time in the tumor bed. Chemoembolization causes massive shrinkage due to ischemia and increasing the local drug intensity and drug exposure. Our study reports the results of multi-agents chemoembolization (MACHEM) in 17 patients bearing massive liver involvement.

From January 1988 we treated 17 patients (5 HCCs, 7 large bowell carcinomas, 1 gastric cancer, 1 ocular melanoma, 1 pancreas, 1 soft tissue sarcoma, 1 carcinoid) using a transfemoral approach to cannulate the celiac axis and then the hepatic artery. The catheter was advanced into the vessel responsible for the majority of the tumor blood supply and a mixture of Gelfoam, radiopaque contrast media, followed by chemotherapy (mitomycin 10 mg/sqm, cisplatin 20 mg/sqm, epirubicin 20 mg/sqm) mixed to LUF was injected until vascular stasis occurred. After chemoembolization, analgesics and anti-pyretics were administered. Liver function tests were monitored daily.

Objective tumor regression was observed in 11 out 15 full evaluable patients; the median duration of survival was 9.5 months. Within 8 weeks shrinkage, due to development of necrosis, appeared in the tumors. One patient with high levels of 5-HIAA due to carcinoid, demonstrated more than 75% decreasing in urinary excretion. In 6 patients out 8 with CEA elevation a clear reduction was documented as well in 2 HCCs out 5 with alfa-fetoprotein elevation.

The palliation of HCC and metastatic liver disease have been extremely disappointing. Systemic chemotherapy produces in HCC a response rate of no more than 20% and does not increase the median survival. Venook obtained 24% of PRs and liquefaction in 35 out 50 HCC treated with chemoembolization. Some results have been also demonstrated in the treatment of metastatic liver tumors by Carrasco, Daniels and Modiano. Moertel stressed that chemoembolization could be incorporated in the initial management of carcinoid. Because of the difference in chemoembolization protocols it is difficult to compare the relative efficacy of this tool, although encouraging response rates have been reported in palliation of bulky tumors. In our study Gelfoam given before LUF and antineoplastic agents mixture produce a distal arteriolar occlusion and this would facilitate the migration of the polychemotherapy emulsion toward the tumor. Our MACHEM program has been shown to have significant activity even in heavily pretreated patients with an acceptable toxicity. We conclude that hepatic arterial chemoembolization will be improved by mean of better combination of chemotherapy with embolizing agents in well selected patients.