title: Benefit of adjuvant interferon alfa-2b (IFN-α) therapy in melanoma patients with high serum MMP-8 levels.
abstract: Matrix metalloproteinases (MMPs) are important enzymes in tissue turnover and various inflammatory processes. In this study, it was evaluated whether serum MMP-8 can predict the response to adjuvant interferon alfa-2b (IFN-α) therapy in patients with operated high-risk cutaneous melanoma. Pre-treatment sera from 460 patients with stage IIB-IIIC melanoma were analyzed for MMP-8. The patients were randomized after surgery to adjuvant IFN-α for 12 or 24 months (n = 313) or observation only (n = 147). The median serum MMP-8 level was used to classify the patients into a low MMP-8 (n = 232) and a high MMP-8 (n = 228) group. In the high MMP-8 subgroup, IFN-α therapy significantly improved relapse-free survival (RFS). RFS was 36.8 months in patients with high MMP-8 levels receiving IFN-α therapy, whereas RFS for those with high MMP-8 levels with observation only was 10.6 months (P = 0.027). Median overall survival for patients with high MMP-8 and observation only was 36.7 versus 71.7 months in those receiving IFN-α (P = 0.13). In a multivariate model, IFN-α therapy was a significant predictor of favorable RFS (HR 0.74; 95 % CI 0.55-0.99; P = 0.048), after adjustment for pre-treatment MMP-8 (HR 1.17; 95 % CI 0.88-1.55; P = 0.28), gender (HR 1.16; 95 % CI 0.86-1.56; P = 0.32), age (HR 1.00; 95 % CI 1.00-1.02; P = 0.12), ulceration (HR 1.09; 95 % CI 0.81-1.46; P = 0.58), and the presence of node metastases (HR 1.36; 95 % CI 1.17-1.58; P < 0.0001). In conclusion, patients with high serum MMP-8 levels may benefit from adjuvant IFN-α therapy, but this observation should be further investigated.
authors.affiliation: Department of Oncology and Radiotherapy, Turku University Hospital, POB 52, 20521, Turku, Finland, pia.vihinen@tyks.fi.
authors.forename: Pia
authors.initials: P
authors.lastname: Vihinen
authors.forename: Taina
authors.initials: T
authors.lastname: Tervahartiala
authors.forename: Timo
authors.initials: T
authors.lastname: Sorsa
authors.forename: Johan
authors.initials: J
authors.lastname: Hansson
authors.forename: Lars
authors.initials: L
authors.lastname: Bastholt
authors.forename: Steinar
authors.initials: S
authors.lastname: Aamdal
authors.forename: Ulrika
authors.initials: U
authors.lastname: Stierner
authors.forename: Seppo
authors.initials: S
authors.lastname: Pyrhönen
authors.forename: Kari
authors.initials: K
authors.lastname: Syrjänen
authors.forename: Johan
authors.initials: J
authors.lastname: Lundin
authors.forename: Micaela
authors.initials: M
authors.lastname: Hernberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000097:blood*; D008545:Melanoma / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D020784:Matrix Metalloproteinase 8