Does pegylated interferon α-2b confer additional benefit in the adjuvant treatment of high-risk melanoma?
Department of Medicine, University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA 15213, USA.Nature Clinical Practice Oncology (Impact Factor: 8). 02/2009; 6(2):70-1. DOI: 10.1038/ncponc1297
High-dose interferon (IFN)alpha-2b has shown benefits in the adjuvant treatment of melanoma, but relapse-free and overall survival remain poor, despite the use of chemotherapy, vaccines, and combinations of these modalities. Questions remain in relation to the relative importance of dose, route and duration of immunotherapy needed to prevent relapse and improve survival. Our understanding of STAT signaling, the role of dendritic and T cells and of circulating cytokine profiles in this benefit of IFN therapy have yet to be deployed clinically. The EORTC 18991 trial analyzed whether pegylated IFNalpha-2b delivered for up to 5 years could improve tolerability and efficacy of IFN. The study demonstrated an improvement in a subset of patients with microscopic disease, but not in those with gross nodal involvement. The potential role of this agent needs to be examined in relation to the long-term control of relapse. Assessment of the molecular, immunological, and antiangiogenic effects of the various forms of pegylated IFN will be critical to identification of the best future applications for these modalities.
Article: Adjuvants and autoimmunity. Lupus[Show abstract] [Hide abstract]
ABSTRACT: Some adjuvants may exert adverse effects upon injection or, on the other hand, may not trigger a full immunological reaction. The mechanisms underlying adjuvant adverse effects are under renewed scrutiny because of the enormous implications for vaccine development. In the search for new and safer adjuvants, several new adjuvants were developed by pharmaceutical companies utilizing new immunological and chemical innovations. The ability of the immune system to recognize molecules that are broadly shared by pathogens is, in part, due to the presence of special immune receptors called toll-like receptors (TLRs) that are expressed on leukocyte membranes. The very fact that TLR activation leads to adaptive immune responses to foreign entities explains why so many adjuvants used today in vaccinations are developed to mimic TLR ligands. Alongside their supportive role, adjuvants were found to inflict by themselves an illness of autoimmune nature, defined as 'the adjuvant diseases'. The debatable question of silicone as an adjuvant and connective tissue diseases, as well as the Gulf War syndrome and macrophagic myofaciitis which followed multiple injections of aluminium-based vaccines, are presented here. Owing to the adverse effects exerted by adjuvants, there is no doubt that safer adjuvants need to be developed and incorporated into future vaccines. Other needs in light of new vaccine technologies are adjuvants suitable for use with mucosally delivered vaccines, DNA vaccines, cancer and autoimmunity vaccines. In particular, there is demand for safe and non-toxic adjuvants able to stimulate cellular (Th1) immunity. More adjuvants were approved to date besides alum for human vaccines, including MF59 in some viral vaccines, MPL, AS04, AS01B and AS02A against viral and parasitic infections, virosomes for HBV, HPV and HAV, and cholera toxin for cholera. Perhaps future adjuvants occupying other putative receptors will be employed to bypass the TLR signaling pathway completely in order to circumvent common side effects of adjuvant-activated TLRs such as local inflammation and the general malaise felt because of the costly whole-body immune response to antigen.Lupus 11/2009; 18(13):1217-25. DOI:10.1177/0961203309345724 · 2.20 Impact Factor
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ABSTRACT: Malignant melanoma is a rare disease in Taiwan with an incidence rate of 0.65/100,000. Excessive exposure to ultraviolet radiation is not associated with most Taiwanese melanoma cases. Acral lentiginous melanoma comprises 58% of cutaneous melanoma. Advanced disease is seen in 50% of cases. Surgery, including resection of the primary melanoma, sentinel lymph nodes that may harbor microscopic metastasis, clinically abnormal lymph nodes, and selected distant metastases, is the most important treatment. Lymphatic mapping and sentinel lymph node biopsy has changed the clinical stage in 22.2% of our patients. Adjuvant high-dose interferon significantly prolongs progression-free survival. However, its use in Taiwan is limited by its substantial toxicity. The prognosis of metastatic disease remains poor with a median survival of 12 months. In the past, chemotherapy alone was the most common treatment modality for metastatic disease. Recently biochemotherapy has been more commonly utilized to treat patients with metastatic melanoma.Chang Gung medical journal 11/2010; 33(6):602-12.
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ABSTRACT: Since the pivotal cooperative group trials in the 1980's-90's,, high-dose interferon (HDI) has been the standard of adjuvant therapy. Despite multiple other trials evaluating potential new therapies in melanoma, HDI remains the only FDA-approved therapy for stage IIB and III melanoma. Initial reports from the more recent phase III international trials of modifications of the original HDI regimen linked the appearance of autoimmunity with improved outcomes of disease. Trials of high-dose interleukin-2, many years earlier, reported anecdotal observations that were consistent with the hypothesis that autoimmunity and clinical benefit of immunotherapies of melanoma are linked with one another. The only prospectively conducted study examining the appearance of clinical and laboratory evidence of autoimmunity during HDI therapy was published by Gogas and colleagues, demonstrating statistically significant impact on relapse-free survival and overall survival. Retrospectively conducted studies of different intermediate dosage regimens of interferon (IFN) have not fully confirmed the linkage of serological evidence of autoimmunity and improved survival outcomes. With the emergence of new immunotherapies in treatment of melanoma, this review highlights the importance of autoimmunity for future applications in melanoma and reviews significant differences of past studies evaluating the appearance of autoimmunity during IFN therapy in high-risk melanoma.Seminars in Immunopathology 07/2011; 33(4):385-91. DOI:10.1007/s00281-011-0247-y · 7.75 Impact Factor
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