Serum TNF-α, B2M and sIL-2R levels are biological correlates of outcome in adjuvant IFN-α2b treatment of patients with melanoma.
OBJECTIVE
There are no biological markers available to predict outcome in melanoma patients treated with adjuvant interferon-alpha (IFN-α). The clinical activity of IFN-α 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-α-treated patients to find potential biological markers for response or toxicity.


METHODS
In a prospective randomized trial, 66 stages II and III melanoma patients underwent an induction treatment of 10 MU IFN α2b s.c. 5 ×/week, followed by either 5 MU or 10 MU IFN α2b s.c. 3 ×/week for a total of 2 years. Serial measurements of serum IL-1β, IL-2, sIL-2R, IL-6, IL-10, TNF-α and β-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-α levels correlated with toxicity. In patients with relapse, significantly lower levels of TNF-α 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-α, B2M and sIL-2R revealed a positive predictive value for relapse of 82.9% in the multivariate analyses.


CONCLUSIONS
Low TNF-α levels are negatively associated with relapse-free survival. Conversely, high TNF-α 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-α2b treatment.
Hofmann
Maja A
MA
Department of Dermatology and Allergy, Skin Cancer and Melanoma Center, Charité, Universitätsmedizin Berlin, Berlin, Germany. maja.hofmann@charite.de
Kiecker
Felix
F
Küchler
Ingeborg
I
Kors
Christian
C
Trefzer
Uwe
U
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007378:Interleukins / Q000097:blood; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011446:Prospective Studies; D015375:Receptors, Interleukin-2 / Q000097:blood*; D011994:Recombinant Proteins; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D055815:Young Adult; D001613:beta 2-Microglobulin / Q000097:blood*
D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007378:Interleukins; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D001613:beta 2-Microglobulin
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