Intraarterial combined immunochemotherapy for unresectable hepatocellular carcinoma: preliminary results

Abstract

An important objective for patients with unresectable hepatocellular carcinoma (HCC) is the development of effective chemotherapy. We administered a combination of biological response modifiers and anticancer agents to 24 patients with unresectable HCC. Each case had an implanted infuser port which was connected to a catheter placed in the hepatic artery for the intraarterial (i.a.) administration of chemotherapy. The following agents were administered to each patient: recombinant interleukin-2 (800,000 JRU/day infused i.a. continuously for 6 days/week); OK-432 (5 KE injected i.a. twice in 4 weeks and i.m. three times per week); Adriamycin (10 mg injected i.a. twice in 4 weeks); cyclophosphamide (300 mg injected i.a. twice in 4 weeks), and famotidine (40 mg/day administered orally). Objective response was assessed according to tumor size measured by computed tomography and angiography before and after treatment. We observed a complete response (CR) in 4, partial response (PR) in 3, minor response (MR) in 7, no change (NC) in 7, and progressive disease (PD) in 3. The response rate (CR+PR+MR) was 58.3%. The overall 2-year survival rate was 52%. The 2-year survival rate of the responders (CR+PR+MR) was 80%, while that of the non-responders (NC+PD) was 0%. There was a significant difference between the responders and non-responders in respect to survival rate (P < 0.05). The percentages of CD25+ cells, CD56+ cells, and Leu7-CD16+ cells and NK activity in the peripheral blood showed a significant increase following the regimen. Serum levels of tumor necrosis factor alpha TNF alpha rose after the initiation of OK-432. TNF alpha levels were higher in the responders than in the non-responders. Adverse effects included high fever (all patients) and severe transient hypotension (15 patients) that was controlled by conservative therapy. Combined immunochemotherapy administered intraarterially may be a new strategy for treating unresectable HCC.

Hepatic arterial infusion in hepatocellular carcinoma: a single center experience

“…Moreover, immunotherapy has also been studied in HCC, including the administration of immunotherapeutic agents as HAI (ref. [43][44][45] ). Future studies should also investigate whether the HAI of cytotoxic agents suppresses the host immune response to a lesser extent than systemic chemotherapy.…”

Intra-arterial interleukin-12 gene delivery combined with chemoembolization: anti-tumor effect in a rabbit hepatocellular carcinoma (HCC) model

“…These can be activated by some immunotherapy agents through direct damage or modulation of surface antigens by chemotherapy. Mitomycin also can eliminate the suppressor cells or suppressor factors in the blood or effusion, resulting in augmented anti-tumor activity of the activated immunopotentiating cells, especially T-cells (32,33). Maataoui et al (34) studied the antitumor effect of TACE based on mitomycin alone and in combination with different immune therapy in an HCC animal model.…”