Article

Does pegylated interferon alpha-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
Source: PubMed

ABSTRACT 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.

0 Followers
 · 
58 Views
  • [Show abstract] [Hide abstract]
    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 · 6.48 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Cancer immunotherapy encompasses a wide range of treatment modalities that harness the anti-tumor effects of the immune system. Some immunotherapies broadly activate the immune system while others precisely target distinct tumor antigens. Because of this heterogeneity, the side effects associated with immunotherapy can be mild and localized or more severe and systemic. Areas covered: Cytokines, adoptive cellular therapies and vaccines are the most commonly used immunotherapies for the treatment of a number of malignancies and have been used for many decades. Checkpoint blockade has recently emerged as a promising immunotherapy. The biggest benefits of immunotherapy have been demonstrated in melanoma, renal cell carcinoma and hematologic malignancies. Emerging data are highlighting the potential for broad applicability of immunotherapy in a number of solid and hematologic malignancies. Expert opinion: Immunotherapies are slowly becoming integrated into the standard of care in cancer treatment. Promising results using immunotherapy have been reported demonstrating complete remissions and cures in many patients with aggressive malignancies. The complexity and cost of engineering and administering of some forms of immunotherapy limit their use to distinct patient populations. High-throughput and cost-effective techniques are being used to broaden the applications of immunotherapy to treat cancer patients.
    Expert Opinion on Drug Safety 05/2013; 12(5). DOI:10.1517/14740338.2013.795944 · 2.74 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Merkel cell carcinoma (MCC) is a rare and highly aggressive skin cancer associated with the Merkel cell polyomavirus (MCV). As MCC cell lines show oncogene addiction to the MCV T antigens, pharmacologic interference of the large T antigen (LTA) may represent an effective therapeutic approach for this deadly cancer. In this study, we investigated the effects of IFNs on MCC cell lines, especially on MCV-positive (MCV(+)) lines. Type I IFNs (i.e., Multiferon, a mix of different IFN-α subtypes, and IFN-β) strongly inhibited the cellular viability. Cell-cycle analysis showed increased sub-G fractions for these cells upon IFN treatment indicating apoptotic cell death; these effects were less pronounced for IFN-γ. Notably, this inhibitory effect of type I IFNs on MCV(+) MCC cell lines was associated with a reduced expression of the MCV LTA as well as an increased expression of promyelocytic leukemia (PML) protein, which is known to interfere with the function of the LTA. In addition, the intratumoral application of Multiferon resulted in a regression of MCV(+) but not MCV(-) MCCs in vivo. Together, our findings show that type I IFNs have a strong antitumor effect, which is at least in part explained by modulation of the virally encoded LTA.
    Cancer Research 03/2012; 72(8):2120-8. DOI:10.1158/0008-5472.CAN-11-2651 · 9.28 Impact Factor