Serum interleukin-6 as a prognostic biomarker in patients with metastatic melanoma.
ABSTRACT Interleukin-6 (IL-6) is an immunomodulatory cytokine produced by both normal cells and tumor cells, including melanoma cells. The specific biological function of IL-6 in melanoma is unknown. The present study examined whether the serum concentration of IL-6 can predict prognosis in patients with metastatic melanoma. IL-6 was measured by ELISA in serum samples from 103 patients with metastatic melanoma obtained before IL-2-based immunotherapy. Patients with metastatic melanoma had higher serum IL-6 than healthy individuals (median 3.4 ng/l, range 0.3-93 ng/l vs. median 1.4 ng/l, range 0.25-22.5 ng/l, P<0.0001). Pretreatment serum IL-6 was elevated in 43% of the patients. Patients with elevated pretreatment serum IL-6 had shorter overall survival (OS) compared with patients with normal serum IL-6 (P<0.0002). The median OS was 10.8 months [95% confidence interval (CI): 8.86-13.46] in patients with normal serum IL-6 compared with 4.5 months (95% CI: 3.04-7.39) in patients with elevated serum IL-6. Multivariate Cox analysis showed that serum IL-6 [hazard ratio (HR)=1.82, 95% CI: 1.19-2.78, P=0.006] and serum lactate dehydrogenase (HR=2.02, 95% CI: 1.31-3.11, P=0.001) were independent prognostic biomarkers of OS. A combination variable of elevated serum IL-6 and elevated serum lactate dehydrogenase almost quadrupled the risk of early death (HR=3.67, 95% CI: 2.17-6.20, P<0.0001) compared with patients with normal serum levels of these two biomarkers. Elevated serum IL-6 is an independent prognostic biomarker of short OS in patients with metastatic melanoma. A larger retrospective study is ongoing to confirm the findings. To validate serum IL-6 further as a prognostic biomarker, a prospective study is required.
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ABSTRACT: Interleukin-6 (IL-6) is a pleiotropic cytokine with significant functions in the regulation of the immune system. As a potent pro-inflammatory cytokine, IL-6 plays a pivotal role in host defense against pathogens and acute stress. However, increased or deregulated expression of IL-6 significantly contributes to the pathogenesis of various human diseases. Numerous preclinical and clinical studies have revealed the pathological roles of the IL-6 pathway in inflammation, autoimmunity, and cancer. Based on the rich body of studies on biological activities of IL-6 and its pathological roles, therapeutic strategies targeting the IL-6 pathway are in development for cancers, inflammatory and autoimmune diseases. Several anti-IL-6/IL-6 receptor monoclonal antibodies developed for targeted therapy have demonstrated promising results in both preclinical studies and clinical trials. Tocilizumab, an anti-IL-6 receptor antibody, is effective in the treatment of various autoimmune and inflammatory conditions notably rheumatoid arthritis. It is the only IL-6 pathway targeting agent approved by the regulatory agencies for clinical use. Siltuximab, an anti-IL-6 antibody, has been shown to have potential benefits treating various human cancers either as a single agent or in combination with other chemotherapy drugs. Several other anti-IL-6-based therapies are also under clinical development for various diseases. IL-6 antagonism has been shown to be a potential therapy for these disorders refractory to conventional drugs. New strategies, such as combination of IL-6 blockade with inhibition of other signaling pathways, may further improve IL-6-targeted immunotherapy of human diseases.Pharmacology [?] Therapeutics 09/2013; · 7.79 Impact Factor
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ABSTRACT: Fludeoxyglucose F 18 positron emission tomography/computed tomography (PET/CT) has been invaluable in the assessment of melanoma throughout the course of the disease. As with any modality, the studies are incomplete and more information will be gleaned as our experience progresses. Additionally, it is hoped that a newer PET agent in the pipeline will give us even greater success in the identification and subsequent treatment of melanoma. This article aims to examine the utilization of PET/CT in the staging, prognostication, and follow-up of melanoma while providing the physicians who order and interpret these studies practical guidelines and interpretive pitfalls.Radiologic Clinics of North America 09/2013; 51(5):865-79. · 1.95 Impact Factor