Twelve RCTs (5,206 patients) were included. The authors also report the results of an additional RCT with 880 patients.
Recurrence-free survival (14 comparisons from 12 RCTs).
IFN-alpha significantly reduced the odds of recurrence by 17%. The HR was 0.83 (95% CI: 0.77, 0.90, P=0.000003). The absolute difference in recurrence-free survival was 7% (95% CI: 4, 9). No significant heterogeneity was detected (P=0.4). The test for trend suggested some influence of IFN dose (P=0.02), but after excluding the very low dose studies the trend was no longer significant (P=0.2). Tests suggested an increased effect with increased total IFN dose (P=0.05), but there was no significant trend for longer duration of treatment (P=0.6).
Overall survival (13 comparisons from 11 RCTs).
IFN-alpha improved overall survival but the improvement was not statistically significant. The HR was 0.93 (95% CI: 0.85, 1.02, P=0.1). The absolute difference in survival was 3% (95% CI: 0, 6). No significant heterogeneity was detected (P=0.9). Tests showed no significant trend for increased dose (P=0.8), increased total scheduled dose (P=1.0), or longer duration of treatment (P=0.6).
Studies that directly compared two different doses of IFN (2 RCTs).
One RCT compared a dose of 20 MU decreasing to 10 MU with a dose of 3 MU; the other RCT compared 10 and 5 MU. Neither RCT showed any significant difference between high- and low-dose IFN.
The inclusion of one trial of IFN-alpha versus vaccine with the two trials of high-dose IFN-alpha given for one year showed no clear survival benefit. The HR was 0.85 (95% CI: 0.72, 1.01, P=0.06).