Interferon therapy study

Gunsar E, Akarca US, Ersoz G, Kobak AC, Karasu Z, Yuce G, liter T, Batur Y (2005) Two-year interferon therapy with or without ribavirin in chronic delta hepatitis. Antivir Ther 10 721-726 Habersetzer E, Boyer N, MarceUin P, Badly F, Ahmed SN, Alam J, Benhamou JP, Trepo C (2000) A pdot study of recombinant interferon beta-la for the treatment of chronic hepatitis C. Liver 20 437 41... 

Surgery remains the mainstay of treatment for localized disease. Approximately 30% of patients present with metastatic disease. Although nephrectomy has traditionally not been recommended in the context of metastatic disease, except in cases of pain or hemorrhage due to local tumor burden, two recent phase III studies have reported modest improvement in durations of survival when carefully selected patients undergo nephrectomy followed by interferon therapy. The larger of the two studies reported a median survival advantage of 3 months. 

Two recent trials report that treatment of patients earlier in the course of MS— after a first acute clinical demyelinating event—is of value [9,10]. The results of these studies suggest that interferon-P-la may delay the development of a second bout of demyelination. These reports may influence decisions regarding the timing of interferon therapy, but the inconvenience of medication requiring injection, treatment-related side effects, cost, and the lack of evidence of an important long-term benefit of interferon-P will deter many specialists from starting treatment earlier in the course of the disease. 

Patti F, Amato MP, Filippi M, Gallo P, Trojano M, Comi GC (2004) A double blind placebo-controlled phase II, add-on study of cyclophosphamide (CTX) for 24 months in patients affected by multiple sclerosis on a background therapy with interferon-beta study denomination CYCLIN. J Neurol 223(1) 69—71. 

Interferon The occurrence of AIH during the treatment of chronic hepatitis B with interferon has already been described (13), as have manifestations and new episodes of inflammation caused by interferon in patients with AIH and chronic hepatitis C. (32, 66, 78) The indication for interferon therapy has to be considered with caution in cases of chronic viral hepatitis with concurrent AIH or autoimmune cholangitis it should also be monitored with great care. In replicative chronic hepatitis B, B/D or C, the chronic viral hepatitis constitutes the major factor - whereas AIH is seen as a concomitant phenomenon. Immunosuppressive therapy is not indicated. In addition, as recent studies show, there are also differences within the HCV infection itself for example, 90% of HCV carriers in Japan and 20% of those in the USA and Germany are at the same time HGV carriers (GB-C). The GB-C and HGV hepatitis viruses are designated defective because they require completion by the helper virus HCV. (s. p. 450)... 

Iron removal Increased iron and ferritin levels are found in approx. 30% of patients with chronic hepatitis B or C. Several studies have shown that the success rate of interferon therapy is reduced in the presence of elevated liver iron values. This is attributed to the fact that iron overload inhibits not only lymphocyte proliferation, but also the function of killer cells and B cells as well as the production of antibodies. Iron plays a role in the formation of free radicals and the occurrence of dangerous lipid peroxidations, (s. pp 68, 401) Furthermore, iron, like oxygen radicals, promotes fibrogenesis. Iron removal leads to an improvement in laboratory parameters and better response to interferon-a therapy. (217, 243) On the other hand, the iron level is reduced as a result of successful IFN therapy. In the case of a higher serum iron status before the initiation of interferon therapy, venesections at one week intervals should be considered, if necessary until normal laboratory values (iron, ferritin, transferrin saturation) have been restored. During interferon therapy, a low-iron diet is advisable, as is the consumption of 2 x 1 cup of black tea (in the morning and at noon) to reduce iron absorption through chelate formation ( cheap, free of side effects and useful )- (s. p. 625) Silymarin also leads to iron mobilization due to chelate formation. 

Tanaka, H., Tsukuma, H., Kasahara, A., Hayashi, N., Yoshihara, H., Masnzawa, M., Kanda, T., Kashiwagi, T., Inoue, A., Kato, M., Oshima, A., Klnoshita, Y., Kamada, T. Effect of interferon therapy on the incidence of hepatocellular carcinoma and mortality of patients with chronic hepatitis C a retrospective cohort study of 738 patients. Int. J. Cancer 2000 87 741-749... 

Soriano V, Bravo R, Samaniego JG, Gonzalez J, Odriozola PM, Arroyo E, Vicario JL, Castro A, Cohnenero M, CarbaUo E, et al. CD4-I- T-lymphocyto-penia in HIV-infected patients receiving interferon therapy for chronic hepatitis C. HIV-Hepatitis Spanish Study Group. AIDS 1994 8(ll) 1621-2. 

Toxicities for the interferon therapy were common and severe in a majority of the patients at some point during therapy and necessitated dose reductions and/or delays during both the induction and maintenance phases of the study. Dose modifications were required for dose-limiting constitutional symptoms, hematologic toxicity, and hepatic toxicities, but 74% of the patients were able to complete the year of therapy in an outpatient setting. 

The frequency and severity of toxicity seen with HDI in the adjuvant setting and the lack of overall survival benefit has raised several important questions (1) Are the toxicities associated with HDI treatment worth the potential benefits for patients (2) What are the mechanism(s) and best standard(s) of care for patients who experience interferon toxicity (3) Is the regimen/schedule of interferon used in the initial positive trial (HDI) necessary to achieve the benefits seen in this study Aggressive toxicity evaluation and individnalized management is essential to help preserve quality of life in those individuals receiving interferon therapy. 

Because of the associated toxicity and adverse effects seen with interferon-a therapy there has been worldwide concern about the usefulness of this intensive adjuvant therapy for melanoma despite the possible benefits in relapse-free and overall survival. A subsequent report from the cooperative group study demonstrated a quality-of-life benefit with interferon therapy based on the quality-of-life-adjusted survival analysis. This analysis calculates the quality-of-life-adjusted years gained as a result of interferon-a treatment or the clinical benefit of time without toxicities and without disease. 

In an attempt to provide the benefit of aldesleukin therapy without the serious side effects, a number of studies have evaluated continuous-infusion aldesleukin therapy, and lower-dose aldesleukin alone or with chemotherapy and interferon therapy. Response rates have been promising, but survival has not been significantly affected. At this time, direct head-to-head comparisons of various dosing schedules and regimens are needed to determine the optimum approach to aldesleukin therapy in metastatic melanoma. The coadministration of LAK cells with aldesleukin does not appear to significantly improve clinical response. Although some studies have suggested improved response with coadministration of TILs with recombinant IL-2, the therapy is technically difficult and costly, and the overall clinical benefit has not been clearly demonstrated. 

The volume of distribution is similar for both IFN-a and IFN-y, ranging from 12 to 40 liters [158,161]. Although this volume is not physiological, it is approximately 20% to 60% of body weight. Information regarding IFN-P has not been established. On the other hand, the penetration of interferons across the human blood-brain barrier has been actively studied. Partially purined [162], natural [163], and recombinant [162] interferons do not readily cross the blood-brain barrier intact after intravenous, intramuscular, or subcutaneous administration. These data suggest that direct effect of parent interferon for the nervous system is not responsible for the occurrence of neurotoxicity, a common side effect of interferon therapy. 

Faiss S, Pape UF, Bohmig M, et al. (2003) Prospective, randomized, multicenter trial on the antiproliferative effect of lanreotide, interferon alfa, and their combination for therapy of metastatic neuroendocrine gastroenteropancreatic tumors—The International Lanreotide and Interferon Alfa Study Group. J Clin Oncol 21 2689-2696... 

Balan V Nelson DR, Sulkowski MS, Everson GT, Lambiase LR, Wiesner RH, Dickson RC, Post AB, Redfleld RR, Davis GL, Neumann AU, Osborn BE, Ereimuth WW, Subramanian GM (2006) A Phase I/II study evaluating escalating doses of recombinant human albumin-interferon-alpha fusion protein in chronic hepatitis C patients who have failed previous interferon-alpha-based therapy, Antivir Ther 11 35 5... 

BriUanti S, Garson J, FoU M, Whitby K, Deaville R, Masci C, MigUoU M, Barbara L (1994) A pilot study of combination therapy with ribavirin plus interferon alfa for interferon alfa-resistant chronic hepatitis C. Gastroenterology 107 812-817... 

Rahal JJ, Anderson J, Rosenberg C, Reagan T, Thompson LL (2004) Effect of interferon-alpha2b therapy on St. Louis viral meningoencephalitis chnical and laboratory results of a pilot study. 1 Infect Dis 190 1084-1087... 

Santantonio T, Niro GA, Sinisi E, Leandro G, Insalata M, Guastadisegni A, Facciorusso D, Gravinese E, Andriulli A, Pastore G (2002) Lamivudine/interferon combination therapy in anti-HBe positive chronic hepatitis B patients a controlled pilot study. J Hepatol 36 799-804... 

Polynucleotides. Polynucleotides are potent interferon inducers. A mismatched, double-stranded synthetic polyribonucleotide ampligen and the double-stranded acids, polyadenylic-polyuridylic acid and polyinosinic-polycytidylic acids have been widely studied for cancer therapy(ii). Although these materials elicit excellent activity with murine rodents, therapeutic effects are dramatically decreased within primates. 

The bDNA assay was used to study the clinical impact of coinfection and the effects of interferon-a and ribavirin therapy of HGV/GBV-C RNA levels in patients chronically infected with both HGV/GBV-C and HCV (Lau et al, 1997 Martinot et al., 1997 McHutchinson et al., 1997). There were no differences in the clinical, biochemical, or histological features of the coinfected patients compared with those infected with HCV alone. Interferon-a treatment caused a marked but usually transient reduction in serum levels of HGV/GBV-C RNA, and ribavirin caused a modest reduction of viral load of 0.5 to 1 log10. 

Alimena, G. et al., Interferon alpha-2b as therapy for Ph -positive chronic myelogenous leukemia A study of 82 patients treated with intermittent or daily administration, Blood, 72, 642, 1988. 

Organ transplants The safety and efficacy of peginterferon alfa-2b alone or in combination with ribavirin capsules for the treatment of hepatitis C in patients who have received liver or other organ transplants have not been studied. Preliminary data indicate that interferon alpha therapy may be associated with an increased rate of kidney graft rejection. Liver graft rejection also has been reported, but a causal... 

Jacobs LD, Beck RW, Simon JH, Kinkel RP, Brownschei-dle CM, Murray TJ et al. Intramuscular interferon beta-1 a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med 2000 343(13) 898-904. 

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