M. Oka et al., INTRAARTERIAL COMBINED IMMUNOCHEMOTHERAPY FOR UNRESECTABLE HEPATOCELLULAR-CARCINOMA - PRELIMINARY-RESULTS, Cancer immunology and immunotherapy, 38(3), 1994, pp. 194-200
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.