title: 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.
authors.affiliation: Second Department of Surgery, Yamaguchi University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Oka
authors.forename: S
authors.initials: S
authors.lastname: Hazama
authors.forename: S
authors.initials: S
authors.lastname: Yoshino
authors.forename: K
authors.initials: K
authors.lastname: Shimoda
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: R
authors.initials: R
authors.lastname: Shimizu
authors.forename: K
authors.initials: K
authors.lastname: Yano
authors.forename: M
authors.initials: M
authors.lastname: Nishida
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D015738:Famotidine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage; D007694:Killer Cells, Natural / Q000276:immunology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000628:therapy*; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010844:Picibanil / Q000008:administration & dosage; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D010844:Picibanil; D015738:Famotidine; D004317:Doxorubicin; D003520:Cyclophosphamide