Phase II randomized trial of autologous formalin-fixed tumor vaccine for postsurgical recurrence of hepatocellular carcinoma.
OBJECTIVE
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).


METHODS
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 large-scale randomized trial.
Kuang
Ming
M
Department of Hepatobiliary Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Peng
Bao G
BG
Lu
Ming D
MD
Liang
Li J
LJ
Huang
Jie F
JF
He
Qiang
Q
Hua
Yun P
YP
Totsuka
Saeri
S
Liu
Shu Q
SQ
Leong
Kam W
KW
Ohno
Tadao
T
D000368:Aged; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D018572:Disease-Free Survival; D005260:Female; D005557:Formaldehyde; D006801:Humans; D008111:Liver Function Tests; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology*; D016019:Survival Analysis; D013997:Time Factors
D019496:Cancer Vaccines; D005557:Formaldehyde