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

• Published in: Clinical cancer research Vol. 10; no. 5; pp. 1574 - 1579
• Main Authors: MING KUANG, PENG, Bao G, OHNO, Tadao, LU, Ming D, LIANG, Li J, HUANG, Jie F, QIANG HE, HUA, Yun P, TOTSUKA, Saeri, LIU, Shu Q, LEONG, Kam W
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.03.2004
• Subjects: Aged; Antineoplastic agents; Biological and medical sciences; Cancer Vaccines - adverse effects; Cancer Vaccines - therapeutic use; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - surgery; Disease-Free Survival; Female; Formaldehyde; Humans; Liver Function Tests; Liver Neoplasms - mortality; Liver Neoplasms - pathology; Liver Neoplasms - surgery; Male; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - immunology; Pharmacology. Drug treatments; Survival Analysis; Time Factors; Tumors; Prevention; Randomization; Relapse; Phase II trial; Digestive diseases; Hepatic disease; Hepatocellular carcinoma; Autologous system; Vaccine; Malignant tumor
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-03-0071

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 large-scale randomized trial.