Systemic and regional treatment of primary carcinoma of the liver

Abstract

IX. Summary Primary cancer of the liver is rare in the United States but much more common in Asian and African populations. The median survival after diagnosis for symptomatically treated patients is less than 4 months. Surgical resection is the treatment of choice whenever possible. The reported resectability rate varies from zero to 30%, and the operative mortality from 12.5 to 34%. Although the majority of cases die with recurrent disease, patients whose lesion can be resected have the longest survival (5-year survival rate = 10 to 15%). Radiotherapy has been shown to be of limited benefit for primary carcinoma of the liver. In the past, systemic chemotherapy using a variety of single agents or various combinations produced a low response rate and did not prolong survival times. Two recent reports gave great hopes. In an uncontrolled study (74), 7 of 19 patients had objective response to combinations of 5FU and BCNU, and three patients were in complete remission for 3, 4 and 6 years. In another study (82), all 11 patients responded to adriamycin (median survival = 8 months), with three exhibiting complete tumor regression and surviving 8, 9 and 13 months. Regional chemotherapy to the liver has the advantages of achieving higher local concentrations of drug, prolonging the contact of drug and tumor cells, and reducing systemic toxicity. Several reports showed that intra-arterial infusion of chemotherapeutic agents (5FU, FUDR, methotrexate and mitomycin) can give response in 50 to 75% of the cases, and prolonging survival over untreated patients or patients receiving other routes of chemotherapy. Studies of both animal and human tumors have demonstrated that both primary and metastatic tumors in the liver receive their blood supplies almost exclusively from the hepatic arterial system, whereas normal liver tissue has a double supply: the hepatic artery(s) and the portal vein. Thus, deliberate ligation of the hepatic artery has been used as treatment of primary tumors of the liver. Excluding patients with cirrhosis, massive involvement of the liver and far advanced hepatic decompensation, the overall operative mortality associated with hepatic artery ligation is about 19%, with 4% directly attributable to ligation of the artery. Although selective necrosis of tumor nodules has been demonstrated after ligation of the hepatic artery, there is always a shell of viable malignant cells left at the periphery. Thus, several series have administered chemotherapeutic agents either to branches of the portal vein or to the distal hepatic artery to prevent tumor regrowth. However, currently for primary carcinoma of the liver, there is no definite evidence that hepatic artery ligation, with or without added infusion chemotherapy to the liver, gives better response and/or survival results than infusion chemotherapy to the hepatic artery alone. Thus, carefully controlled and randomized prospective clinical trials are urgently needed to compare these different treatment modalities. Other therapeutic approaches such as infusion chemotherapy via the portal vein, ligation of portal vein branches, and liver transplantation have not shown definite benefit. On the other hand, 2 cases of spontaneous regression of hepatoma and 3 cases of documented cure after 5FU or 5FU-BCNU combination chemotherapy have been reported. In conclusion, primary carcinoma of the liver is a virulent and fatal disease. For non-resectable lesions, regional and systemic chemotherapeutic treatment is available. With the availability of adriamycin and newer combinations of effective agents, the outlook for such patients may be greatly improved.