INTRAARTERIAL COMBINED IMMUNOCHEMOTHERAPY FOR UNRESECTABLE HEPATOCELLULAR-CARCINOMA - PRELIMINARY-RESULTS

An important objective for patients with unresectable hepatocellular c arcinoma (HCC) is the development of effective chemotherapy. We admini stered a combination of biological response modifiers and anticancer a gents 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. Th e following agents were administered to each patient: recombinant inte rleukin-2 (800000 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 w eek); Adriamycin (10 mg injected i.a. twice in 4 weeks); cyclophospham ide (300 mg injected i.a. twice in 4 weeks), and famotidine (40 mg/day administered orally). Objective response was assessed according to tu mor size measured by computed tomography and angiography before and af ter treatment. We observed a complete response (CR) in 4, partial resp onse (PR) in 3, minor response (MR) in 7, no change (NC) in 7, and pro gressive disease (PD) in 3. The response rate (CR+PR+MR) was 58.3%. Th e overall 2-year survival rate was 52%. The 2-year survival rate of th e responders (CR+PR+MR) was 80%, while that of the non-responders (NCPD) was 0%. There was a significant difference between the responders and non-responders in respect to survival rate (P <0.05). The percenta ges of CD25(+) cells, CD56(+) cells, and Leu7(-) CD16(+) cells and NK activity in the peripheral blood showed a significant increase followi ng the regimen. Serum levels of tumor necrosis factor alpha TNF alpha rose after the initiation of OK-432. TNF alpha levels were higher in t he responders than in the non-responders. Adverse effects included hig h fever (all patients) and severe transient hypotension (15 patients) that was controlled by conservative therapy. Combined immunochemothera py administered intraarterially may be a new strategy for treating unr esectable HCC.