Phase II trial of pegylated interferon-alpha 2b in patients with advanced renal cell carcinoma.
ABSTRACT Pegylated interferon (IFN) has a longer serum half-life compared with standard IFN, and this allows for weekly dosing. In this study, the efficacy and toxicity of pegylated IFN was assessed in patients with metastatic renal cell carcinoma (mRCC).
Thirty-two patients with previously untreated mRCC were treated with pegylated IFN-alpha 2b in a prospective, single-arm phase II trial. Pegylated IFN was given by subcutaneous administration on a weekly schedule at a dose of 4.5 microg/kg.
Of the 32 assessable patients, 29 (91%) had a nephrectomy previously, and none had been treated previously with systemic therapy. Forty-one percent had good-risk, 53% had intermediate-risk, and 6% had poor-risk features per Memorial Sloan-Kettering Cancer Center risk criteria. The best response was a complete response (CR) in 1 patient (3%). Nine patients (28%) had a partial response. Fifteen patients (47%) had stable disease. The median progression-free survival (PFS) was 5 months (95% CI, 3-7 months), and median overall survival was 31 months (95% CI, 18 months to not reached). Five patients had a prolonged PFS of > or = 17 months, 1 of whom achieved a CR. There were no grade 4 toxicities; primary grade 3 toxicities were hematologic (11 of 32 patients; 34%) and fatigue (4 of 32 patients; 13%).
Pegylated IFN administered weekly has antitumor activity in patients with mRCC with predominantly good- and intermediate-risk features. This study suggests comparable efficacy and safety compared with standard IFN-alpha.
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- "Type I interferons (IFN) are a family of cytokines produced locally in response to viral, bacterial and protozoan infections   and have early important effects in DC maturation, NK-cell activation, TH1 differentiation and CTL priming   . Type I interferons are therefore important in immune responses against tumors   and IFN-␣ is now used in the treatment of various cancers such as melanoma and renal cell carcinoma  . Recently, several reports have focused on either the generation of monocyte-derived DC with GM-CSF and IFN-␣  , or the use of IFN-␣ as a maturation reagent [12,21,22,25]. "
ABSTRACT: Monocyte-derived dendritic cells (DCs) are used as adjuvant cells in cancer immunotherapy and have shown promising results. In order to obtain full functional capacity, these DCs need to be maturated, and the current "gold standard" for this process is maturation with TNF-alpha, IL-1beta, IL-6 and PGE(2) used for generating standard DCs (sDC). Several studies indicate that IFN-alpha might also be important for DC differentiation and maturation. In this study, we tested the effect of IFN-alpha alone or as addition to the gold standard sDC cocktail. We observed that maturation by IFN-alpha differs from sDC maturation: The major phenotypic change after IFN-alpha maturation was dose-dependent up-regulation of CD38 but not CD83, while sDCs expressed the opposite profile with low CD38 and high CD83 expression. Similarly, maturation by Poly I:C leads to CD38high, CD83low DCs indicating a functional relationship between CD38, IFN-alpha and TLR3. Thus, CD38 appear to be a relevant marker for activation by TLR3 or IFN-alpha. Addition of IFN-alpha to the sDC cocktail results in up-regulation of both CD38 and CD83 and improved capacity for induction of autologous T-cell responses despite few other changes in DC phenotype and cytokine secretion. Our observations suggest that IFN-alpha could be included in maturation protocols for clinical grade DCs used for immunotherapy against cancer and should be included if DCs are used for CD8+ T-cell stimulation in vitro.Vaccine 05/2009; 27(16):2213-9. DOI:10.1016/j.vaccine.2009.02.015 · 3.49 Impact Factor
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ABSTRACT: Prostate cancer is the most frequently diagnosed cancer in men in Western countries. Clinically localized disease can be cured with surgery or radiotherapy, but once the disease has advanced or spread, there are no curative treatments. This review examines the potential utility of cytokines, in particular interferon gamma (IFNgamma), in the treatment of clinically advanced prostate cancer.Anticancer research 09/2008; 28(5B):2843-9. · 1.87 Impact Factor