Intraarterial combined immunochemotherapy for unresectable hepatocellular carcinoma : preliminary results

• Published in: Cancer Immunology, Immunotherapy Vol. 38; no. 3; pp. 194 - 200
• Main Authors: OKA, M, HAZAMA, S, YOSHINO, S, SHIMODA, K, SUZUKI, M, SHIMIZU, R, YANO, K, NISHIDA, M, SUZUKI, T
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.05.1994; Springer Berlin Heidelberg
• Subjects: Aged; Antineoplastic agents; Biological and medical sciences; Carcinoma, Hepatocellular - therapy; Combined Modality Therapy; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Cyclophosphamide - administration & dosage; Doxorubicin - administration & dosage; Famotidine - administration & dosage; Female; Humans; Immunity, Cellular; Immunotherapy; Interleukin-2 - administration & dosage; Killer Cells, Natural - immunology; Liver Neoplasms - drug therapy; Liver Neoplasms - therapy; Lymphocyte Subsets - immunology; Male; Medical sciences; Middle Aged; Original; Pharmacology. Drug treatments; Picibanil - administration & dosage; Survival Analysis; Tumor Necrosis Factor-alpha - metabolism; Antineoplastic agent; Human; Drug combination; Immunochemotherapy; Cytokine; Hepatic disease; Malignant tumor; Chemotherapy; Immunostimulant agent; Interleukin 2; Microbial origin; Liver cell carcinoma; Immunotherapy; Unresectable; Digestive diseases; Combined treatment; Intraarterial administration
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/BF01525641

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.