Serum TNF-alpha, B2M and sIL-2R levels are biological correlates of outcome in adjuvant IFN-alpha2b treatment of patients with melanoma.

摘要

PURPOSE: There are no biological markers available to predict outcome in melanoma patients treated with adjuvant interferon-alpha (IFN-alpha). The clinical activity of IFN-alpha is thought to be mediated not only by anti-proliferative effects, but also by induction and modulation of secondary cytokines. We examined serum cytokine levels in IFN-alpha-treated patients to find potential biological markers for response or toxicity. PATIENTS AND METHODS: In a prospective randomized trial, 66 stages II and III melanoma patients underwent an induction treatment of 10 MU IFN alpha2b s.c. 5 x/week, followed by either 5 MU or 10 MU IFN alpha2b s.c. 3 x/week for a total of 2 years. Serial measurements of serum IL-1beta, IL-2, sIL-2R, IL-6, IL-10, TNF-alpha and beta-2 microglobulin (B2M) were taken. Two factorial analysis of repeated measurements (ANOVA) as well as univariate and multivariate analyses was used to identify prognostic factors for relapse and toxicity. RESULTS: TNF-alpha levels correlated with toxicity. In patients with relapse, significantly lower levels of TNF-alpha were detected at baseline and throughout therapy compared with patients without relapse. B2M and sIL-2R showed a significant increase throughout the therapy phase. At baseline, the combination of TNF-alpha, B2M and sIL-2R revealed a positive predictive value for relapse of 82.9% in the multivariate analyses. CONCLUSION: Low TNF-alpha levels are negatively associated with relapse-free survival. Conversely, high TNF-alpha levels are correlated with toxicity but seem to be beneficial to patients with regard to relapse-free survival. B2M and sIL-2R are biological markers of adjuvant IFN-alpha2b treatment.