Last Updated: 2012-01-06 15:13:29 -0400 (Reuters Health)
By David Douglas and Nancy Lapid
NEW YORK (Reuters Health) - Postoperative therapy with interferon alfa-2b doesn't keep hepatitis-related hepatocellular carcinoma (HCC) from recurring, Taiwanese researchers have found.
As Dr. Pei-Jer Chen, who headed the study, told Reuters Health by email, "Interferon alfa 2b adjuvant therapy failed to reduce HCC recurrence or (improve) overall survival in patients receiving surgical resection. Now other combination adjuvant therapies are urgently needed."
In a report this month in Annals of Surgery, Dr. Chen of National Taiwan University College of Medicine, Taipei and colleagues note that although most individual trials of adjuvant interferon in this setting had failed, meta-analyses had suggested that interferon alfa-2b could be of benefit after curative ablation.
To investigate further, the researchers enrolled 268 patients in a randomized trial of adjuvant interferon alfa-2b, or no interferon, after curative surgery. Eighty percent of the patients had hepatitis B virus (HBV) surface antigen; the others had hepatitis C.
During a median follow-up of slightly more than five years, 58% had tumor recurrence and 31% died. Intention-to-treat analysis gave a five-year recurrence-free survival of 44.2% and overall survival of 73.9%.
Overall, the median recurrence-free survival was 42.2 months in the interferon group and 48.6 months in controls. Broken down by etiology, disease-free survival in the interferon and control groups, respectively, was 42.2 and 31.1 months with HCV and 42.4 and 49.1 months with HBV. None of these differences was statistically significant.
As could be expected, side effects were more common with interferon. Treated patients had a significantly higher incidence of leukopenia and thrombocytopenia.
Viral replication was only temporarily suppressed during the treatment, and the researchers suggest that "studies to investigate a more permanent inhibition of HCV replication by pegylated interferon alfa/ribavirin combinations deserve further exploration." For HBV, they add, oral nucleoside analogs may be of use.
Dr. Chen and colleagues began enrolling patients in this trial more than seven years ago. Dr. Yuman Fong from Memorial Sloan-Kettering Cancer Center in New York City, who was not involved in Dr. Chen's study, confirmed for Reuters Health that in the years since that trial was designed, nothing more promising has appeared on the horizon.
It's "very sad," he said in an email, "since 750,000 patients get HCC each year."
If he were doing the study now, Dr. Fong added, he "would take only patients with detectable virus in blood and randomize to current generation antivirals."
Ann Surg 2011