Phase II Randomized Trial of Autologous Formalin-Fixed Tumor Vaccine for Postsurgical Recurrence of Hepatocellular Carcinoma

Abstract

Purpose: We conducted a Phase II clinical trial with randomized patients to determine whether autologous formalin-fixed tumor vaccine (AFTV) protects against postsurgical recurrence of hepatocellular carcinoma (HCC).Experimental Design: Forty-one patients with HCC who had undergone curative resection were randomly allocated to the vaccine treatment (n ‫؍‬ 19) or no adjuvant control group (n ‫؍‬ 22). Three intradermal vaccinations were administered at 2-week intervals beginning 4 -6 weeks after hepatic resection. A delayed-type hypersensitivity test was performed before and after vaccination. Primary and secondary end points are recurrence-free survival and overall survival, respectively. Observation continued until the majority of surviving patients had lived >12 months after the curative resection.Results: In a median follow-up of 15 months, the risk of recurrence in vaccinated patients was reduced by 81% (95% confidence interval, 33-95%; P ‫؍‬ 0.003). Vaccination significantly prolonged the time to first recurrence (P ‫؍‬ 0.003) and improved recurrence-free survival (P ‫؍‬ 0.003) and overall survival rates (P ‫؍‬ 0.01). AFTV played a significant role in preventing recurrence in patients with small tumors. Adverse effects were limited to grade 1 or 2 skin toxicities such as erythema, dry desquamation, and pruritus.Conclusions: AFTV therapy is a safe, feasible, and effective treatment for preventing postoperational recurrence of HCC. Patients with low tumor burdens benefit from the treatment. This treatment should be advanced to a largescale randomized trial.

A Phase I/II Trial Testing Immunization of Hepatocellular Carcinoma Patients with Dendritic Cells Pulsed with Four α-Fetoprotein Peptides

“…© 2006 American Association for Cancer clincancerres.aacrjournals.org Downloaded from colony-stimulating factor, IL-2, and Bacillus Calmette-Guerin (24). Forty-one stage I-IIIa subjects, postcurative resection, were enrolled and randomized; 19 received vaccine.…”

Phase I/IIa trial of fractionated radiotherapy, temozolomide, and autologous formalin-fixed tumor vaccine for newly diagnosed glioblastoma

“…developed an autologous formalin-fixed tumor vaccine (AFTV) for in vivo induction of killer lymphocytes, 5,16 suppression of recurrence of hepatocellular carcinoma after primary resection, 12 and treatment of recurrent GBM in a pilot clinical trial. 6 Our previous prospective clinical trial for preliminary evaluation of the efficacy of AFTV concomitant with fractionated radiotherapy (FRT), but not with concomitant TMZ, in patients with newly diagnosed GBM (study identification no.…”

Identification and analysis of tumour-associated antigens in hepatocellular carcinoma

“…Over the past decade, a number of clinical trials have been conducted to examine the potential for the activation of tumour-specific T cells in HCC patients, many have shown biological activity and a subset has shown antitumour efficacy (Iwashita et al, 2003;Butterfield, 2004;Kuang et al, 2004). Recent reports on clinical trial of AFP-based vaccine indicated that spontaneous AFP-specific immunologic responses had been induced in vaccinated HCC patients.…”