Rationale and indications for perfusion in liver tumors: Current data

Abstract

Current DataSince Novermber, 1981, 50 patients (predominantly those with metastases of coiorectal carcinomas) have been treated in our clinic by an isolated regional chemotherapy on an average of 9 months after the primary operation. The mortality rate was 8%.The eytostatic drugs applied alone or in combination were 5fluorouracil (5-FU) (300-1,250 mg) and mitomycin C (5-50 mg) in 46 patients, and 5-FU, mitomycin C, and cisplatin (50 mg) in 4 patients. The course of the disease was observed in 41 patients. The median survival was 14 months, 24 months in 11 patients still living, and 12.5 months in those patients who died. An additional treatment with cycles of an intraarterial infusion therapy seeemed to extend the survival time (7.5 months without additional treatment, 18 months with additional treatment). Nine (22%) of 41 patients had a complete remission, and 28 (68%), a partial remission. Lung metastases and/or local tumor recurrences arose in 40% of the patients with secondary liver tumors.We consider the very high eytostatic drug concentrations in the infusion circuit and the additional perfusion of the portal vein to be the advantages of isolated liver perfusion (ILP). Certainly, this therapy can be applied only once, and ILP must he completed by another means of treatment.Patients with liver tumors who do not receive treatment seldom live longer than 1 89 years, and only 2-4 months in advanced stages [1][2][3]. So far, no patient has been registered who lived longer than 5 years. Systemic chemotherapy has hardly improved the results.Intraarterial infusion, first mentioned by Klopp et al. [4], increases the local cytostatic drug concentration considerably and, thus, exploits the dose-effect relationship. In 1951, Biermann [5] inserted a catheter selectively into the hepatic artery. The first experiments of isolated regional perfusion were performed by Ryan [6] and Creech et al. [7]. In the early 1960's, the idea was taken up by other study groups [8][9][10][11]. Aust and Ausman [8] first tried isolated liver perfusion (ILl?) on humans; however, the method was not developed any further and gained importance only in recent years [12].We applied ILP for the first time in November, 1981, on a patient with liver metastases of a rectal carcinoma [ 13,14], only after we had sufficiently perfected the technique in experimental studies [15]. A caval catheter with 2 lumina, which we introduced, considerably simplified the operative procedure.

A Phase I Trial of Isolated Hepatic Perfusion (IHP) Using 5-FU and Oxaliplatin in Patients with Unresectable Isolated Liver Metastases from Colorectal Cancer

“…Aigner et al 21 reported safe doses of 5-FU between 700 and 1,100 mg delivered with hyperthermia as an hour-long perfusion in 32 patients. Schwemmle et al 22 reported 5-FU (300–1,250 mg) delivered in combination with mitomycin C as an isolated hepatic perfusion in 50 patients. This discrepancy between our MTD and the doses previously given likely represent temporal differences in the studies.…”

Regional chemotherapy of non-resectable liver metastases from colorectal cancer - literature and institutional review

“…In this trial of the ALM, the trial arm with 5-HAI-FUDR had similar response rates as HAI with 5-FU plus FA, but a lower survival time at a remarkable hepatic toxicity that was not present in HAI or systemic therapy with 5-FU plus FA (Table 2) [55]. Various trials involving stop-flow infusion, microsphere infusion, or isolated liver perfusion have been conducted, but none of those trials improved the median survival time versus "conventional" HAI or systemic treatment [5, 25,65,68,69], although the number of long-term survivors after isolated liver perfusion (+HAI) was remarkable [2].…”

“…The response rate was 48% and survival time 19 months. The High-effort techniques applying either HAI with microspheres [68,69], stop-flow techniques [25] or isolated liver perfusion [2,65] may increase response rates compared with conventional HAI, but a significant prolongation of median survival times has not been proven.…”

Regional Treatment for Unresectable Malignant Hepatic Tumors: An Overview of Isolated Hepatic Perfusion

“…In their series, median survival was 8 months, and no response data were reported. Schwemmle et al [36] observed a 22% complete response and a 68% partial response rate after IHP with 5-FU/MMC/cisplatin. In contrast, Hafstrome et al [37] reported in 1994 their results of IHP with melphalan and cisplatin in 29 patients and observed a response rate of only 20% and a mortality rate of as much as 14%.…”