Systemic and arterial infusion chemotherapy for metastatic liver cancer.

SYSTEMIC CHEMOTHERAPY Despite the enormity of the problems presented by the manifold forms of metastatic neoplasm of the liver, there is a scant literature available on the effects of systemic cancer chemotherapeutic agents for these tumors and no co-operative clinical trials have been mounted by the National Cancer Institute or other co-operative clinical chemotherapy groups. For the most part, reports in the literature of the effects of systemic anticancer drugs on metastatic liver cancers are but a part of investigations of the eff ects of the drugs on primary cancers arising from diverse anatomie sites, i.e. gastrointestina1 neoplasms. Without doubt, in the majority of these reports of the clinical responses noted in patients with gastrointestinal cancers (i.e. colorectal, stomach, pancreas, gallbladder and bile ducts, carcinoid tumors) and because of the extremely high incidence of clinically significant liver metastases, the main indicator lesion to therapeutic response in these reports relates to measurements of metastatic deposits in the liver, using direct measurements of liver size, serial liver function tests and serial angiography and liver stans. Thus, it is reasonable to compare or equate the responses of systemic cancer chemotherapy in gastrointestinal neoplasms, as reported in the literature, to the response rate of hepatic metastases in patients with these neoplasms. Indeed, Jaffe et al.’ noted in a study of 390 patients with untreated hepatic metastases that the progress of the cancer within the liver appeared to be the dominant influence on survival regardless of the presence of metastases in other sites. In the early application of chemotherapeutic drugs to metastatic cancers of the liver it was assumed that these tumors were resistant to these agents. Little or no response was noted in poorly documented studies using alkylating agents and early antimetabolites: methotrexate and o-mercaptopurine. With the advent of 5fluorouracil (5-FU), numerous reports have documented objective tumor regression of metastatic liver cancers arising from primary sites in the gastrointestinal tract. Response rates have averaged about 20% (range 8-85%)” with median duration of response about 3-5 months and no increase of survival.” Various dose schedules of 5-FU that have been studied include: daily loading intravenous (IV) doses, prolonged IV infusion, weekly doses of 15 mg/kg, etc. There appears to be no advantage in the therapeutic index of one dose schedule over the other. Nor has oral 5-FU any special advantage over IV 5-FU-it is less predictable. In a report by Moertel and Reitmeie? in which the site of the primary indicator lesion was detailed, they found a response rate of 24% in 118 patients with liver metastases from colorectal cancer. In addition to 5-FU, numerous antimetabolites, alkylating agents, antibiotics and other agents have been used singly and in combination with 5-FU but have shown no therapeutic advantage over 5-FU alone. Regretably, most of these studies have been poorly formulated. Other metastatic liver neoplasms amenable to treatment with systemic chemotherapy include (1) breast cancer-combination of 5-FU. methotrexate, cyclophosphamide (cytoxan), (2) lung cancer (oat cell)-alkylating agents, (3) Islet cel1 cancer of the pancreas-