Benefit of adjuvant interferon alfa-2b (IFN-α) therapy in melanoma patients with high serum MMP-8 levels
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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.
KeywordsAdjuvant interferon Melanoma MMP Prognosis Serum Survival
American Joint Committee on Cancer
Analysis of variance
v-Raf murine sarcoma viral oncogene homolog B1
Coefficent of variation
Eastern cooperative oncology group
Head and neck squamous cell carcinomas
Interferon stimulated gene
Kirsten rat sarcoma viral oncogene homolog
Neuroblastoma RAS viral oncogene homolog
The Nordic Adjuvant IFN-α study was supported by a research Grant from Schering-Plough (now Merck), the Radiumhemmet Research Funds, and the Stockholm City Council (Drs Hansson, Bastholt, Aamdal, Stierner, Hernberg). The current serum analyses were supported by a research Grant from Schering-Plough (now Merck), the Southwest Funds of the Finnish Cancer Research Society, the Turku University Hospital EVO grant (projects 13040 and 13041) (Drs Vihinen, Pyrhönen, Syrjänen, Hernberg), and the Helsinki University Hospital EVO Grant (project TYH 2012210 and 2013353) (Dr Sorsa). The invaluable input of all investigators participating in the Nordic Adjuvant Trial is gratefully acknowledged.
Conflict of interest
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