Combined intraarterial 5‐fluorouracil and subcutaneous interferon‐α therapy for advanced hepatocellular carcinoma with tumor thrombi in the major portal branches

Abstract

BACKGROUNDThe prognosis of hepatocellular carcinoma (HCC) invading into the major branches of the portal vein (Vp3) is extremely poor.METHODSEleven consecutive patients with HCC and Vp3 were treated with 2–6 cycles of a “basic” combination therapy consisting of continuous arterial infusion of 5‐fluorouracil (450–500 mg/day, for the initial 2 weeks) and subcutaneous injection of interferon‐α (5 million international units, 3 times/week, 4 weeks). In the first 3 patients, methotrexate (90 mg/day 1 of every week), cisplatin (10 mg/day), and leucovorin (30 mg/days 2 and 3 of every week) also were administered for the initial 2 weeks (“full” regimen).RESULTSIn 8 (73%) of 11 patients, an objective response (complete response [CR] or partial response [PR]) was observed with marked regression of tumor and decrease in tumor markers. The use of the full regimen was associated with objective response in all patients; instead, they developed thrombocytopenia or leukopenia. In the subsequent 8 patients with basic regimen, 5 patients showed CR (2 cases) or PR (3 cases; objective response rate, 63%), and leukopenia was observed only in 1 patient.CONCLUSIONSSimple combination therapy with subcutaneous interferon‐α and intraarterial 5‐fluorouracil therefore is a promising treatment modality for intractable HCC with Vp3. Cancer 2002;94:435–42. © 2002 American Cancer Society.

Treatment of hepatocellular carcinoma with major portal vein thrombosis by combined therapy with subcutaneous interferon-α and intra-arterial 5-fluorouracil; role of type 1 interferon receptor expression

“…Based on this background, we experienced a patient with advanced HCC and lung metastasis, who was successfully treated with a combination therapy of IFN-a and tegafur/uracil (UFT) . In addition, we recently reported the outstanding effects of intra-arterial 5-fluorouracil (5-FU) combined with subcutaneous IFN-a for advanced HCC with tumour thrombi in the major portal branches, since 1997 (Sakon et al, 2002). Based on our results, the marked effects and acceptable toxicity of our therapy in HCC patients with extremely poor prognosis suggest that IFN-a/5-FU combination therapy is a promising treatment regimen.…”

“…This was a single arm open label study, based on our pervious report (Sakon et al, 2002). Between December 1997 and December 2003, 124 patients with advanced HCC and tumour thrombi in the major branches of the portal vein and multiple liver metastasis (Vp3 or 4, IM3) were diagnosed in our department.…”

“…(9) total bilirubin less than 1.4 g dl À1 , (10) serum BUN less than 30 mg dl À1 , (11) serum creatinine less than 1.5 mg dl À1 , (12) successful implantation of intra-arterial catheter and drug delivery system, and (13) a performance status of level 0 -2 (Eastern Cooperative Oncology Group, ECOG). These eligibility criteria were based on our previous report (Sakon et al, 2002). All patients signed informed consent documents approved by the institutional review board attesting to the fact that they were aware of the investigational nature of the study and were willing to try the combination therapy.…”

“…The present study is an extension to our previous work (Sakon et al, 2002), in which we examined the clinical effects of the combination therapy of subcutaneous IFN-a and arterial infusion of 5-FU in 55 patients with HCC associated with Vp3 and investigated whether the response to such therapy is influenced by the expression level of IFNAR2.…”

Combination therapy with PEG-IFN-α and 5-FU inhibits HepG2 tumour cell growth in nude mice by apoptosis of p53

“…However, none of these local treatments are suitable for patients whose HCC has invaded the portal vein. Recent studies have suggested that these patients may be effectively treated by combination therapy involving subcutaneous (s.c.) administration of interferon (IFN)-a and intrahepatic administration of 5-fluorouracil (5-FU) (Sakon et al, 2002;Obi et al, 2006). A Phase II trial has also revealed that continuous 5-FU infusion combined with thrice-weekly treatment with IFN-a effectively treats HCC, perhaps because the drugs together play a neoadjuvant role (Patt et al, 2003).…”