Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial

• Published in: The Lancet (British edition) 2000-09, Vol.356 (9232), p.802-807
• Main Authors: Takayama, Tadatoshi, Sekine, Teruaki, Makuuchi, Masatoshi, Yamasaki, Susumu, Kosuge, Tomoo, Yamamoto, Junji, Shimada, Kazuaki, Sakamoto, Michiie, Hirohashi, Setsuo, Ohashi, Yasuo, Kakizoe, Tadao
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Biological and medical sciences; Cancer; Carcinoma, Hepatocellular - surgery; Carcinoma, Hepatocellular - therapy; Clinical trials; Disease-Free Survival; Ethanol; Hepatectomy; Humans; Immune system; Immunology; Immunotherapy; Immunotherapy - adverse effects; Immunotherapy - methods; Interleukin-2 - administration & dosage; Interleukin-2 - therapeutic use; Liver cancer; Liver Neoplasms - surgery; Liver Neoplasms - therapy; Lymphocytes; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - prevention & control; Pharmacology. Drug treatments; Postoperative Period; Survival; Tumors
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(00)02654-4

Postsurgical recurrence of hepatocellular carcinoma (HCC) is frequent and fatal. Adoptive immunotherapy is active against HCC. We assessed whether postoperative immunotherapy could lower the frequency of recurrence. Between 1992 and 1995, we did a randomised trial in which 150 patients who had undergone curative resection for HCC were assigned adoptive immunotherapy (n=76) or no adjuvant treatment (n=74). Autologous lymphocytes activated vitro with recombinant interleukin-2 and antibody to CD3 were infused five times during the first 6 months. Primary endpoints were time to first recurrence and recurrence-free survival and analyses were by intention to treat. 76 patients received 370 (97%) of 380 scheduled lymphocyte infusions (mean cell number per patient 7·1 × 10 10 [SD 2·1]; CD3 and HLA-DR cells 78% [16]), and none had grade 3 or 4 adverse events. After a median follow-up of 4·4 years (range 0·2–6·7), adoptive immunotherapy decreased the frequency of recurrence by 18% compared with controls (45% [59] vs 57% [77]) and reduced the risk of recurrence by 41% (95% Cl 12–60, p=0·01). Time to first recurrence in the immunotherapy group was significantly longer than that in the control group (48% [37–59] vs 33% [22–43] at 3 years, 38% [22–54] vs 22% [11–34] at 5 years; p=0·008). The immunotherapy group had significantly longer recurrence-free survival (p=0·01) and disease-specific survival (p=0·04) than the control group. Overall survival did not differ significantly between groups (p=0·09). Adoptive immunotherapy is a safe, feasible treatment that can lower recurrence and improve recurrence-free outcomes after surgery for HCC.