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Interferons in the Treatment of Solid Tumors

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Cytokines and Cancer

Part of the book series: Cancer Treatment and Research ((CTAR,volume 126))

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References

  1. Isaacs A, Lindenmann J. Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci. 1957;147:258–267.

    Article  PubMed  CAS  Google Scholar 

  2. Pestka S, Langer JA, Zoon KC, et al. Interferons and their actions. Annu Rev Biochem. 1987;56:727–777.

    Article  PubMed  CAS  Google Scholar 

  3. Gresser I. Production of interferon by suspensions of human leucocytes. Proc Soc Exp Biol Med. 1961;108:799–803.

    PubMed  CAS  Google Scholar 

  4. Peterson OP, Yui L. Preparation of Interferon From Cultures of Chick Fibroblasts Treated With Inactivated Vaccinia Virus. Fed Proc Transl Suppl. 1964;23:545–546.

    PubMed  CAS  Google Scholar 

  5. Wheelock EF. Interferon-like Virus Inhibitor Induce in Human Leukocytes by Phytohemagglutinin. Science. 1965;149:310–311

    Article  CAS  Google Scholar 

  6. Cantell K, Hirvonen S, Kauppinen HL, et al. Production of interferon in human leukocytes from normal donors with the use of Sendai virus. Methods Enzymol. 1981;78:29–38.

    Article  PubMed  CAS  Google Scholar 

  7. Rubinstein M, Rubinstein S, Familletti PC, et al. Human leukocyte interferon purified to homogeneity. Science. 1978;202:1289–1290.

    Article  PubMed  CAS  Google Scholar 

  8. Taniguchi T, Fujii-Kuriyama Y, Muramatsu M. Construction and identification of a bacterial plasmid containing the human fibroblast interferon gene sequences. Proc Japan Acad. 1979;55B:464–469

    Article  Google Scholar 

  9. Nagata S, Mantei N, Weissmann C. The structure of one of the eight or more distinct chromosomal genes for human interferon-alpha. Nature. 1980;287:401–408.

    Article  PubMed  CAS  Google Scholar 

  10. Manns MP. Current state of interferon therapy in the treatment of chronic hepatitis B. Semin Liver Dis. 2002;22:7–13.

    Article  PubMed  Google Scholar 

  11. Horowski R. Multiple sclerosis and interferon beta-1b, past, present and future. Clin Neurol Neurosurg. 2002;104:259–264.

    Article  PubMed  Google Scholar 

  12. Tyring SK. Treatment of condyloma acuminatum with interferon. Semin Oncol. 1988;15:35–40.

    PubMed  CAS  Google Scholar 

  13. Jonasch E, Haluska FG. Interferon in oncological practice: review of interferon biology, clinical applications, and toxicities. Oncologist. 2001;6:34–55.

    Article  PubMed  CAS  Google Scholar 

  14. Aguet M, Grobke M, Dreiding P. Various human interferon alpha subclasses cross-react with common receptors: their binding affinities correlate with their specific biological activities. Virology. 1984;132:211–216.

    Article  PubMed  CAS  Google Scholar 

  15. Allen G, Diaz MO. Nomenclature of the human interferon proteins. J Interferon Cytokine Res. 1996;16:181–184.

    Article  PubMed  CAS  Google Scholar 

  16. Owerbach D, Rutter WJ, Shows TB, et al. Leukocyte and fibroblast interferon genes are located on human chromosome 9. Proc Natl Acad Sci USA. 1981;78:3123–3127.

    Article  PubMed  CAS  Google Scholar 

  17. LaFleur DW, Nardelli B, Tsareva T, et al. Interferon-kappa, a novel type I interferon expressed in human keratinocytes. J Biol Chem. 2001;276:39765–39771.

    Article  PubMed  CAS  Google Scholar 

  18. Billiau A, Heremans H, Vermeire K, et al. Immunomodulatory properties of interferongamma. An update. Ann N Y Acad Sci. 1998;856:22–32.

    Article  PubMed  CAS  Google Scholar 

  19. Gresser I, Maury C, Brouty-Boye D. Mechanism of the antitumor effect of interferon in mice. Nature. 1972;239:167–168.

    Article  PubMed  CAS  Google Scholar 

  20. Gresser I, Belardelli F. Endogenous type I interferons as a defense against tumors. Cytokine Growth Factor Rev. 2002;13:111–118.

    Article  PubMed  CAS  Google Scholar 

  21. Fearon DT, Locksley RM. The instructive role of innate immunity in the acquired immune response. Science. 1996;272:50–53.

    Article  PubMed  CAS  Google Scholar 

  22. Chouaib S, Asselin-Paturel C, Mami-Chouaib F, et al. The host-tumor immune conflict: from immunosuppression to resistance and destruction. Immunol Today. 1997;18:493–497.

    Article  PubMed  CAS  Google Scholar 

  23. Belardelli F, Ferrantini M. Cytokines as a link between innate and adaptive antitumor immunity. Trends Immunol. 2002;23:201–208.

    Article  PubMed  CAS  Google Scholar 

  24. Le Bon A, Schiavoni G, D'Agostino G, et al. Type I interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo. Immunity. 2001;14:461–470.

    Article  PubMed  Google Scholar 

  25. Paquette RL, Hsu NC, Kiertscher SM, et al. Interferon-alpha and granulocyte-macrophage colony-stimulating factor differentiate peripheral blood monocytes into potent antigen-presenting cells. J Leukoc Biol. 1998;64:358–367.

    PubMed  CAS  Google Scholar 

  26. Lindahl P, Gresser I, Leary P, et al. Interferon treatment of mice: enhanced expression of histocompatibility antigens on lymphoid cells. Proc Natl Acad Sci USA. 1976;73:1284–1287.

    Article  PubMed  CAS  Google Scholar 

  27. Miettinen M, Sareneva T, Julkunen I, et al. IFNs activate toll-like receptor gene expression in viral infections. Genes Immun. 2001;2:349–355.

    Article  PubMed  CAS  Google Scholar 

  28. Luft T, Pang KC, Thomas E, et al. Type I IFNs enhance the terminal differentiation of dendritic cells. J Immunol. 1998;161:1947–1953.

    PubMed  CAS  Google Scholar 

  29. Mailliard RB, Son YI, Redlinger R, et al. Dendritic cells mediate NK cell help for Thl and CTL responses: two-signal requirement for the induction of NK cell helper function. J Immunol. 2003;171:2366–2373.

    PubMed  CAS  Google Scholar 

  30. Parlato S, Santini SM, Lapenta C, et al. Expression of CCR-7, MIP-3beta, and Th-I chemokines in type I IFN-induced monocyte-derived dendritic cells: importance for the rapid acquisition of potent migratory and functional activities. Blood. 2001;98:3022–3029.

    Article  PubMed  CAS  Google Scholar 

  31. Santini SM, Lapenta C, Logozzi M, et al. Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice. J Exp Med. 2000;191:1777–1788.

    Article  PubMed  CAS  Google Scholar 

  32. Siegal FP, Kadowaki N, Shodell M, et al. The nature of the principal type 1 interferon producing cells in human blood. Science. 1999;284:1835–1837.

    Article  PubMed  CAS  Google Scholar 

  33. Cella M, Jarrossay D, Facchetti F, et al. Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat Med. 1999;5:919–923.

    Article  PubMed  CAS  Google Scholar 

  34. Zou W, Machelon V, Coulomb-L'Hermin A, et al. Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells. Nat Med. 2001;7:1339–1346.

    Article  PubMed  CAS  Google Scholar 

  35. Kadowaki N, Antonenko S, Lau JY, et al. Natural interferon alpha/beta-producing cells link innate and adaptive immunity. J Exp Med. 2000;192:219–226.

    Article  PubMed  CAS  Google Scholar 

  36. Ito T, Amakawa R, Inaba M, et al. Differential regulation of human blood dendritic cell subsets by IFNs. J Immunol. 2001;166:2961–2969.

    PubMed  CAS  Google Scholar 

  37. Krug A, Veeraswamy R, Pekosz A, et al. Interferon-producing cells fail to induce proliferation of naive T cells but can promote expansion and T helper 1 differentiation of antigen-experienced unpolarized T cells. J Exp Med. 2003;197:899–906.

    Article  PubMed  CAS  Google Scholar 

  38. Brinkmann V, Geiger T, Alkan S, et al. Interferon alpha increases the frequency of interferon gamma-producing human CD4+ T cells. J Exp Med. 1993;178:1655–1663.

    Article  PubMed  CAS  Google Scholar 

  39. Wenner CA, Guler ML, Macatonia SE, et al. Roles of IFN-gamma and IFN-alpha in IL-12-induced T helper cell-I development. J Immunol. 1996;156:1442–1447.

    PubMed  CAS  Google Scholar 

  40. Rogge L, Barberis-Maino L, Biffi M, et al. Selective expression of an interleukin-12 receptor component by human T helper 1 cells. J Exp Med. 1997;185:825–831.

    Article  PubMed  CAS  Google Scholar 

  41. McRae BL, Picker LJ, van Seventer GA. Human recombinant interferon-beta influences T helper subset differentiation by regulating cytokine secretion pattern and expression of homing receptors. Eur J Immunol. 1997;27:2650–2656.

    Article  PubMed  CAS  Google Scholar 

  42. Marrack P, Kappler J, Mitchell T. Type I interferons keep activated T cells alive. J Exp Med. 1999;189:521–530.

    Article  PubMed  CAS  Google Scholar 

  43. Tough DF, Borrow P, Sprent J. Induction of bystander T cell proliferation by viruses and type I interferon in vivo. Science. 1996;272:1947–1950.

    Article  PubMed  CAS  Google Scholar 

  44. Palmer KJ, Harries M, Gore ME, et al. Interferon-alpha (IFN-alpha) stimulates anti-melanoma cytotoxic T lymphocyte (CTL) generation in mixed lymphocyte tumour cultures (MLTC). Clin Exp Immunol. 2000; 119:412–418.

    Article  PubMed  CAS  Google Scholar 

  45. Carballido JA, Molto LM, Manzano L, et al. Interferon-alpha-2b enhances the natural killer activity of patients with transitional cell carcinoma of the bladder. Cancer. 1993;72:1743–1748.

    Article  PubMed  CAS  Google Scholar 

  46. Parmar S, Platanias LC. Interferons: mechanisms of action and clinical applications. Curr Opin Oncol. 2003;15:431–439.

    Article  PubMed  CAS  Google Scholar 

  47. Wills RJ. Clinical pharmacokinetics of interferons. Clin Pharmacokinet. 1990;19:390–399.

    Article  PubMed  CAS  Google Scholar 

  48. Sama G, Pertcheck M, Figlin R, et al. Phase I study of recombinant beta ser 17 interferon in the treatment of cancer. Cancer Treat Rep. 1986;70:1365–1372.

    Google Scholar 

  49. Rinehart JJ, Malspeis L, Young D, et al. Phase I/II trial of human recombinant interferon gamma in renal cell carcinoma. J Biol Response Mod. 1986;5:300–308.

    PubMed  CAS  Google Scholar 

  50. Shah I, Band J, Samson M, et al. Pharmacokinetics and tolerance of intravenous and intramuscular recombinant alpha 2 interferon in patients with malignancies. Am J Hematol. 1984;17:363–371.

    Article  PubMed  CAS  Google Scholar 

  51. Giannelli G, Antonelli G, Fera G, et al. 2′,5′-Oligoadenylate synthetase activity as a responsive marker during interferon therapy for chronic hepatitis C. J Interferon Res. 1993;13:57–60.

    PubMed  CAS  Google Scholar 

  52. Liberati AM, Horisberger MA, Garofani P, et al. Interferon-alpha-induced biologic modifications in patients with chronic myelogenous leukemia. J Interferon Res. 1994; 14:349–355.

    PubMed  CAS  Google Scholar 

  53. Bezares F, Kohan S, Sacerdote de Lustig E, et al. Treatment strategies for early-stage chronic lymphocytic leukemia: can interferon-inducible MxA protein and tumor necrosis factor play a role as predictive markers for response to interferon therapy? J Interferon Cytokine Res. 1996;16:501–505.

    Article  PubMed  CAS  Google Scholar 

  54. Barthe C, Mahon FX, Gharbi MJ, et al. Expression of interferon-alpha (IFN-alpha) receptor 2c at diagnosis is associated with cytogenetic response in IFN-alpha-treated chronic myeloid leukemia. Blood. 2001;97:3568–3573.

    Article  PubMed  CAS  Google Scholar 

  55. Bukowski RM, Olencki T, Wang Q, et al. Phase II trial of interleukin-2 and interferon-alpha in patients with renal cell carcinoma: clinical results and immunologic correlates of response. J Immunother. 1997;20:301–311.

    Article  PubMed  CAS  Google Scholar 

  56. Der SD, Zhou A, Williams BR, et al. Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. Proc Natl Acad Sci USA. 1998;95:15623–15628.

    Article  PubMed  CAS  Google Scholar 

  57. Sturzebecher S, Wandinger KP, Rosenwald A, et al. Expression profiling identifies responder and non-responder phenotypes to interferon-beta in multiple sclerosis. Brain. 2003;126:1419–1429.

    Article  PubMed  CAS  Google Scholar 

  58. Certa U, Seiler M, Padovan E, et al. Interferon-a sensitivity in melanoma cells: detection of potential response marker genes. Recent Results Cancer Res. 2002;160:85–91.

    PubMed  CAS  Google Scholar 

  59. Stark GR, Kerr IM, Williams BR, et al. How cells respond to interferons. Annu Rev Biochem. 1998;67:227–264.

    Article  PubMed  CAS  Google Scholar 

  60. Pansky A, Hildebrand P, Fasler-Kan E, et al. Defective Jak-STAT signal transduction pathway in melanoma cells resistant to growth inhibition by interferon-alpha. Int J Cancer. 2000;85:720–725.

    Article  PubMed  CAS  Google Scholar 

  61. Wang T, Niu G, Kortylewski M, et al. Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nat Med. 2004;10:48–54.

    Article  PubMed  CAS  Google Scholar 

  62. Lesinski GB, Anghelina M, Zimmerer J, et al. The antitumor effects of IFN-alpha are abrogated in a STATI-deficient mouse. J Clin Invest. 2003;112:170–180.

    Article  PubMed  CAS  Google Scholar 

  63. Kirkwood JM, Farkas DL, Chakraborty A, et al. Systemic interferon-alpha (IFN-alpha) treatment leads to Stat3 inactivation in melanoma precursor lesions. Mol Med. 1999;5:11–20.

    PubMed  CAS  Google Scholar 

  64. Astsaturov I, Petrella T, Bagriacik EU, et al. Amplification of virus-induced antimelanoma T-cell reactivity by high-dose interferon-alpha2b: implications for cancer vaccines. Clin Cancer Res. 2003;9:4347–4355.

    PubMed  CAS  Google Scholar 

  65. Pfeffer LM, Mullersman JE, Pfeffer SR, et al. STAT3 as an adapter to couple phosphatidylinositol 3-kinase to the IFNAR1 chain of the type I interferon receptor. Science. 1997;276:1418–1420.

    Article  PubMed  CAS  Google Scholar 

  66. Yang CH, Murti A, Pfeffer SR, et al. Interferon alpha /beta promotes cell survival by activating nuclear factor kappa B through phosphatidylinositol 3-kinase and Akt. J Biol Chem. 2001;276:13756–61.

    PubMed  CAS  Google Scholar 

  67. Fish EN, Uddin S, Korkmaz M, et al. Activation of a CrkL-stat5 signaling complex by type I interferons. J Biol Chem. 1999;274:571–573.

    Article  PubMed  CAS  Google Scholar 

  68. Takaoka A, Mitani Y, Suemori H, et al. Cross talk between interferon-gamma and — alpha/beta signaling components in caveolar membrane domains. Science. 2000;288:2357–2360.

    Article  PubMed  CAS  Google Scholar 

  69. Gutterman JU. Cytokine therapeutics: lessons from interferon alpha. Proc Natl Acad Sci USA. 1994;91:1198–1205.

    Article  PubMed  CAS  Google Scholar 

  70. Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol. 2001;19:3635–3648.

    PubMed  CAS  Google Scholar 

  71. Moschos SJ, Kirkwood JM, Konstantinopoulos PA. Present status and future prospects for adjuvant therapy of melanoma: time to build upon the foundation of high-dose interferon alfa-2b. J Clin Oncol. 2004;22:11–14.

    Article  PubMed  CAS  Google Scholar 

  72. Kirkwood JM, Strawderman MH, Emstoff MS, et al. Interferon alfa-2b adjuvant therapy of high-risk rejected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol. 1996;14:7–17.

    PubMed  CAS  Google Scholar 

  73. Kirkwood JM, Ibrahim JG, Sondak VK, et al. High-and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. J Clin Oncol. 2000;18:2444–2458.

    PubMed  CAS  Google Scholar 

  74. Livingston PO, Wong GY, Adluri S, et al. Improved survival in stage III melanoma patients with GM2 antibodies: a randomized trial of adjuvant vaccination with GM2 ganglioside. J Clin Oncol. 1994;12:1036–1044.

    PubMed  CAS  Google Scholar 

  75. Kirkwood JM, Ibrahim JG, Sosman JA, et al. High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with rejected stage IIB-III melanoma: results of intergroup trial E1694/S9512/C509801. J Clin Oncol. 2001;19:2370–2380.

    PubMed  CAS  Google Scholar 

  76. 75a. Creagan ET, Dalton RJ, Ahmann DL, et al. Randomized, surgical adjuvant clinical trial of recombinant interferon alfa-2a in selected patients with malignant melanoma. J Clin Oncol. 1995;13:2776–2783.

    PubMed  CAS  Google Scholar 

  77. Cameron DA, Cornbleet MC, Mackie RM, et al. Adjuvant interferon alpha 2b in high-risk melanoma — the Scottish study. Br J Cancer. 2001;84:1146–1149.

    Article  PubMed  CAS  Google Scholar 

  78. Pehamberger H, Soyer HP, Steiner A, et al. Adjuvant interferon alfa-2a treatment in rejected primary stage II cutaneous melanoma. Austrian Malignant Melanoma Cooperative Group. J Clin Oncol. 1998;16:1425–1429.

    PubMed  CAS  Google Scholar 

  79. Grob JJ, Dreno B, de la Salmoniere P, et al. Randomised trial of interferon alpha-2a as adjuvant therapy in rejected primary melanoma thicker than 1.5 mm without clinically detectable node metastases. French Cooperative Group on Melanoma. Lancet. 1998;351:1905–1910.

    Article  PubMed  CAS  Google Scholar 

  80. Cascinelli N, Belli F, MacKie RM, et al. Effect of long-term adjuvant therapy with interferon alpha-2a in patients with regional node metastases from cutaneous melanoma: a randomized trial. Lancet. 2001;358:866–869.

    Article  PubMed  CAS  Google Scholar 

  81. Hancock BW, Wheatley K, Harris S, et al. Adjuvant interferon in high-risk melanoma: the AIM HIGH Study—United Kingdom Coordinating Committee on Cancer Research randomized study of adjuvant low-dose extended-duration interferon Alfa-2a in high-risk rejected malignant melanoma. J Clin Oncol. 2004;22:53–61.

    Article  PubMed  CAS  Google Scholar 

  82. Kleeberg UR, Suciu S, Brocker EB, et al. Final results of the EORTC 18871/DKG 80-1 randomized phase III trial. rIFN-alpha2b versus rIFN-gamma versus ISCADOR M versus observation after surgery in melanoma patients with either high-risk primary (thickness >3 mm) or regional lymph node metastasis. Eur J Cancer. 2004;40:390–402.

    Article  PubMed  CAS  Google Scholar 

  83. Legha SS, Papadopoulos NE, Plager C, et al. Clinical evaluation of recombinant interferon alfa-2a (Roferon-A) in metastatic melanoma using two different schedules. J Clin Oncol. 1987;5:1240–1246.

    PubMed  CAS  Google Scholar 

  84. Kirkwood JM, Ernstoff MS, Davis CA, et al. Comparison of intramuscular and intravenous recombinant alpha-2 interferon in melanoma and other cancers. Ann Intern Med. 1985;103:32–36.

    PubMed  CAS  Google Scholar 

  85. Legha SS. The role of interferon alpha in the treatment of metastatic melanoma. Semin Oncol. 1997;24:S24–S31.

    PubMed  CAS  Google Scholar 

  86. Kirkwood JM, Richards T, Zarour HM, et al. Immunomodulatory effects of high-dose and low-dose interferon alpha2b in patients with high-risk rejected melanoma: the E2690 laboratory corollary of intergroup adjuvant trial E1690. Cancer. 2002;95:1101–1112.

    Article  PubMed  CAS  Google Scholar 

  87. Hakansson A, Gustafsson B, Krysander L, et al. Tumour-infiltrating lymphocytes in metastatic malignant melanoma and response to interferon alpha treatment. Br J Cancer. 1996;74:670–676.

    PubMed  CAS  Google Scholar 

  88. Motzer RJ, Bander NH, Nanus DM. Renal-cell carcinoma. N Engl J Med. 1996;335:865–875.

    Article  PubMed  CAS  Google Scholar 

  89. Quesada JR. Role of interferons in the therapy of metastatic renal cell carcinoma. Urology. 1989;34:80–83.

    Article  PubMed  CAS  Google Scholar 

  90. Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomized controlled trial. Medical Research Council Renal Cancer Collaborators. Lancet. 1999;353:14–17.

    Google Scholar 

  91. Atzpodien J, Kirchner H, Illiger HJ, et al. IL-2 in combination with IFN-alpha and 5-FU versus tamoxifen in metastatic renal cell carcinoma: long-term results of a controlled randomized clinical trial. Br J Cancer. 2001;85:1130–1136.

    Article  PubMed  CAS  Google Scholar 

  92. Pyrhonen S, Salminen E, Ruutu M, et al. Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer. J Clin Oncol. 1999;17:2859–2867.

    PubMed  CAS  Google Scholar 

  93. Flanigan RC, Salmon SE, Blumenstein BA, et al. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med. 2001;345:1655–1659.

    Article  PubMed  CAS  Google Scholar 

  94. Messing EM, Manola J, Wilding G, et al. Phase III study of interferon alpha-NL as adjuvant treatment for resectable renal cell carcinoma: an Eastern Cooperative Oncology Group/Intergroup trial. J Clin Oncol. 2003;21:1214–1222.

    Article  PubMed  CAS  Google Scholar 

  95. Negrier S, Escudier B, Lasset C, et al. Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. Groupe Francais d'Immunotherapie. N Engl J Med. 1998;338:1272–1278.

    Article  PubMed  CAS  Google Scholar 

  96. Mcdermott D, Flaherty L, Clark J: A randomized phase III trial of high dose interleukin-2 (HD IL-2) vs. subcutaneous IL-2/interferon (IFN) in patients with metastatic renal cell carcinoma (abstract 172a). 2001 in Proc Am Soc Clin Oncol.

    Google Scholar 

  97. Atzpodien J, Kirchner H, Jonas U, et al. Interleukin-2-and Interferon Alfa-2a-Based Immunochemotherapy in Advanced Renal Cell Carcinoma: A Prospectively Randomized Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN). J Clin Oncol. 2004;22:1188–1194

    Article  PubMed  CAS  Google Scholar 

  98. Atzpodien J, Kirchner H, Hanninen EL, et al. Interleukin-2 in combination with interferon-alpha and 5-fluorouracil for metastatic renal cell cancer. Eur J Cancer. 1993;29A:S6–S8.

    Article  PubMed  Google Scholar 

  99. Ravaud A, Audhuy B, Gomez F, et al. Subcutaneous interleukin-2, interferon alfa-2a, and continuous infusion of fluorouracil in metastatic renal cell carcinoma: a multicenter phase II trial. Groupe Francais d'Immunotherapie. J Clin Oncol. 1998;16:2728–2732.

    PubMed  CAS  Google Scholar 

  100. Negrier S, Caty A, Lesimple T, et al. Treatment of patients with metastatic renal carcinoma with a combination of subcutaneous interleukin-2 and interferon alpha with or without fluorouracil. Groupe Francais d'Immunotherapie, Federation Nationale des Centres de Lutte Contre le Cancer. J Clin Oncol. 2000;18:4009–4015.

    PubMed  CAS  Google Scholar 

  101. Atzpodien J, Kirchner H, Illiger HJ, et al. IL-2 in combination with IFN-alpha and 5-FU versus tamoxifen in metastatic renal cell carcinoma: long-term results of a controlled randomized clinical trial. Br J Cancer. 2001;85:1130–1136.

    Article  PubMed  CAS  Google Scholar 

  102. Motzer RJ, Schwartz L, Law TM, et al. Interferon alfa-2a and 13-cis-retinoic acid in renal cell carcinoma: antitumor activity in a phase II trial and interactions in vitro. J Clin Oncol. 1995;13:1950–1957.

    PubMed  CAS  Google Scholar 

  103. Sobota V, Bubenik J, Indrova M, et al. Use of cryopreserved lymphocytes for assessment of the immunological effects of interferon therapy in renal cell carcinoma patients. J Immunol Methods. 1997;203:1–10.

    Article  PubMed  CAS  Google Scholar 

  104. Tsavaris N, Baxevanis C, Kosmidis P, et al. The prognostic significance of immune changes in patients with renal cancer, melanoma and colorectal cancer, treated with interferon alpha 2b. Cancer Immunol Immunother. 1996;43:94–102.

    Article  PubMed  CAS  Google Scholar 

  105. Igarashi T, Takahashi H, Tobe T, et al. Effect of tumor-infiltrating lymphocyte subsets on prognosis and susceptibility to interferon therapy in patients with renal cell carcinoma. Urol Int. 2002;69:51–56.

    Article  PubMed  Google Scholar 

  106. Toliou T, Stravoravdi P, Polyzonis M, et al. Natural killer cell activation after interferon administration in patients with metastatic renal cell carcinoma: an ultrastructural and immunohistochemical study. Eur Urol. 1996;29:252–256.

    PubMed  CAS  Google Scholar 

  107. Bukowski RM, Olencki T, Wang Q, et al. Phase II trial of interleukin-2 and interferon-alpha in patients with renal cell carcinoma: clinical results and immunologic correlates of response. J Immunother. 1997;20:301–311.

    Article  PubMed  CAS  Google Scholar 

  108. Noy A. Update in Kaposi sarcoma. Curr Opin Oncol. 2003;15:379–381.

    Article  PubMed  Google Scholar 

  109. Groopman JE, Gottlieb MS, Goodman J, et al. Recombinant alpha-2 interferon therapy for Kaposi's sarcoma associated with the acquired immunodeficiency syndrome. Ann Intern Med. 1984;100:671–676.

    PubMed  CAS  Google Scholar 

  110. Real FX, Oettgen HF, Krown SE. Kaposi's sarcoma and the acquired immunodeficiency syndrome: treatment with high and low doses of recombinant leukocyte A interferon. J Clin Oncol. 1986;4:544–551.

    PubMed  CAS  Google Scholar 

  111. Evans LM, Itri LM, Campion M, et al. Interferon-alpha 2a in the treatment of acquired immunodeficiency syndrome-related Kaposi's sarcoma. J Immunother. 1991;10:39–50.

    Article  PubMed  CAS  Google Scholar 

  112. Krown SE, Gold JW, Niedzwiecki D, et al. Interferon-alpha with zidovudine: safety, tolerance, and clinical and virologic effects in patients with Kaposi sarcoma associated with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med. 1990;112:812–821.

    PubMed  CAS  Google Scholar 

  113. Ho DD, Hartshorn KL, Rota TR, et al. Recombinant human interferon alpha-A suppresses HTLV-III replication in vitro. Lancet. 1985;1:602–604.

    Article  PubMed  CAS  Google Scholar 

  114. Monini P, Carlini F, Sturzl M, et al. Alpha interferon inhibits human herpes virus 8 (HHV-8) reactivation in primary effusion lymphoma cells and reduces HHV-8 load in cultured peripheral blood mononuclear cells. J Virol. 1999;73:4029–4041.

    PubMed  CAS  Google Scholar 

  115. Sidky YA, Borden EC. Inhibition of angiogenesis by interferons: effects on tumor-and lymphocyte-induced vascular responses. Cancer Res. 1987;47:5155–5161.

    PubMed  CAS  Google Scholar 

  116. Reiter Z, Ozes ON, Blatt LM, et al. A possible role for interferon-alpha and activated natural killer cells in remission of AIDS-related Kaposi's sarcoma: in vitro studies. J Acquir Immune Defic Syndr. 1992;5:469–476.

    PubMed  CAS  Google Scholar 

  117. Janson ET, Oberg K. Malignant neuroendocrine tumors. Cancer Chemother Biol Response Modif. 2002;20:463–470.

    PubMed  Google Scholar 

  118. Eriksson B, Oberg K, Aim G, et al. Treatment of malignant endocrine pancreatic tumors with human leukocyte interferon. Lancet. 1986;2:1307–1309.

    Article  PubMed  CAS  Google Scholar 

  119. Veenhof CH, de Wit R, Taal BG, et al. A dose-escalation study of recombinant interferon-alpha in patients with a metastatic carcinoid tumour. Eur J Cancer. 1992;28:75–78.

    Article  PubMed  CAS  Google Scholar 

  120. Eriksson B, Oberg K, Skogseid B. Neuroendocrine pancreatic tumors. Clinical findings in a prospective study of 84 patients. Acta Oncol. 1989;28:373–377.

    Article  PubMed  CAS  Google Scholar 

  121. Oberg K, Eriksson B, Janson ET. Interferons alone or in combination with chemotherapy or other biologicals in the treatment of neuroendocrine gut and pancreatic tumors. Digestion. 1994;55:64–69.

    Article  PubMed  Google Scholar 

  122. Bajetta E, Zilembo N, Di Bartolomeo M, et al. Treatment of metastatic carcinoids and other neuroendocrine tumors with recombinant interferon-alpha-2a. A study by the Italian Trials in Medical Oncology Group. Cancer. 1993;72:3099–3105.

    Article  PubMed  CAS  Google Scholar 

  123. Andreyev HJ, Scott-Mackie P, Cunningham D, et al. Phase II study of continuous infusion fluorouracil and interferon alfa-2b in the palliation of malignant neuroendocrine tumors. J Clin Oncol. 1995;13:1486–1492.

    PubMed  CAS  Google Scholar 

  124. Saltz L, Kemeny N, Schwartz G, et al. A phase II trial of alpha-interferon and 5-fluorouracil in patients with advanced carcinoid and islet cell tumors. Cancer. 1994;74:958–961.

    Article  PubMed  CAS  Google Scholar 

  125. Hughes MJ, Kerr DJ, Cassidy J, et al. A pilot study of combination therapy with interferon-alpha-2a and 5-fluorouracil in metastatic carcinoid and malignant endocrine pancreatic tumors. Ann Oncol. 1996;7:208–210.

    PubMed  CAS  Google Scholar 

  126. Oberg K, Kvols L, Caplin M, et al. Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol. 2004;15:966–973.

    Article  PubMed  CAS  Google Scholar 

  127. Janson ET, Oberg K. Long-term management of the carcinoid syndrome. Treatment with octreotide alone and in combination with alpha-interferon. Acta Oncol. 1993;32:225–229.

    Article  PubMed  CAS  Google Scholar 

  128. Frank M, Klose KJ, Wied M, et al. Combination therapy with octreotide and alpha-interferon: effect on tumor growth in metastatic endocrine gastroenteropancreatic tumors. Am J Gastroenterol. 1999;94:1381–1387.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  130. von Marschall Z, Scholz A, Cramer T, et al. Effects of interferon alpha on vascular endothelial growth factor gene transcription and tumor angiogenesis. J Natl Cancer Inst. 2003;95:437–448.

    Article  Google Scholar 

  131. Zhou Y, Wang S, Yue BG, et al. Effects of interferon alpha on the expression of p2lcipl/wafl and cell cycle distribution in carcinoid tumors. Cancer Invest. 2002;20:348–356.

    Article  PubMed  CAS  Google Scholar 

  132. Zhou Y, Wang S, Gobl A, et al. Inhibition of CDK2, CDK4 and cyclin E and increased expression of p27Kipl during treatment with interferon-alpha in carcinoid tumor cells. J Biol Regul Homeost Agents. 1999; 13:207–215.

    PubMed  CAS  Google Scholar 

  133. Zhou Y, Wang S, Gobl A, et al. Interferon alpha induction of Stat1 and Stat2 and their prognostic significance in carcinoid tumors. Oncology. 2001;60:330–338.

    Article  PubMed  CAS  Google Scholar 

  134. Imam H, Gobl A, Eriksson B, et al. Interferon-alpha induces bcl-2 proto-oncogene in patients with neuroendocrine gut tumor responding to its antitumor action. Anticancer Res. 1997;17:4659–4665.

    PubMed  CAS  Google Scholar 

  135. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003;362:1907–1917.

    Article  PubMed  Google Scholar 

  136. Lai CL, Wu PC, Lok AS, et al. Recombinant alpha 2 interferon is superior to doxorubicin for inoperable hepatocellular carcinoma: a prospective randomized trial. Br J Cancer. 1989;60:928–933.

    PubMed  CAS  Google Scholar 

  137. Lai CL, Lau JY, Wu PC, et al. Recombinant interferon-alpha in inoperable hepatocellular carcinoma: a randomized controlled trial. Hepatology. 1993;17:389–394.

    Article  PubMed  CAS  Google Scholar 

  138. Lin SM, Lin CJ, Hsu CW, et al. Prospective randomized controlled study of interferon-alpha in preventing hepatocellular carcinoma recurrence after medical ablation therapy for primary tumors. Cancer. 2004;100:376–382.

    Article  PubMed  CAS  Google Scholar 

  139. Patt YZ, Hassan MM, Lozano RD, et al. Phase II trial of systemic continuous fluorouracil and subcutaneous recombinant interferon Alfa-2b for treatment of hepatocellular carcinoma. J Clin Oncol. 2003;21:421–427.

    Article  PubMed  CAS  Google Scholar 

  140. Leung TW, Patt YZ, Lau WY, et al. Complete pathological remission is possible with systemic combination chemotherapy for inoperable hepatocellular carcinoma. Clin Cancer Res. 1999;5:1676–1681.

    PubMed  CAS  Google Scholar 

  141. Hoofnagle JH, di Bisceglie AM. The treatment of chronic viral hepatitis. N Engl J Med. 1997;336:347–356.

    Article  PubMed  CAS  Google Scholar 

  142. Yoshida H, Shiratori Y, Moriyama M, et al. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and non-cirrhotic patients with chronic hepatitis C in Japan. IHIT Study Group. Inhibition of Hepatocarcinogenesis by Interferon Therapy. Ann Intern Med. 1999;131:174–181.

    PubMed  CAS  Google Scholar 

  143. Shiratori Y, Shiina S, Teratani T, et al. Interferon therapy after tumor ablation improves prognosis in patients with hepatocellular carcinoma associated with hepatitis C virus. Ann Intern Med. 2003;138:299–306.

    PubMed  Google Scholar 

  144. Murphy D, Detjen KM, Welzel M, et al. Interferon-alpha delays S-phase progression in human hepatocellular carcinoma cells via inhibition of specific cyclin-dependent kinases. Hepatology. 2001;33:346–356.

    Article  PubMed  CAS  Google Scholar 

  145. Yano H, Iemura A, Haramaki M, et al. Interferon alpha receptor expression and growth inhibition by interferon alpha in human liver cancer cell lines. Hepatology. 1999;29:1708–1717.

    Article  PubMed  CAS  Google Scholar 

  146. Shigeno M, Nakao K, Ichikawa T, et al. Interferon-alpha sensitizes human hepatoma cells to TRAIL-induced apoptosis through DR5 upregulation and NF-kappa B inactivation. Oncogene. 2003;22:1653–1662.

    Article  PubMed  CAS  Google Scholar 

  147. Legrand A, Vadrot N, Lardeux B, et al. Study of the effects of interferon a on several human hepatoma cell lines: analysis of the signalling pathway of the cytokine and of its effects on apoptosis and cell proliferation. Liver Int. 2004;24:149–160.

    Article  PubMed  CAS  Google Scholar 

  148. Dunk AA, Novick D, Thomas HC. Natural killer cell activity in hepatocellular carcinoma. In vitro and in vivo responses to interferon. Scand J Gastroenterol. 1987;22:1245–1250.

    Article  PubMed  CAS  Google Scholar 

  149. Malmstrom PU, Busch C, Norlen BJ. Recurrence, progression and survival in bladder cancer. A retrospective analysis of 232 patients with greater than or equal to 5-year follow-up. Scand J Urol Nephrol. 1987;21:185–195.

    Article  PubMed  CAS  Google Scholar 

  150. Torti FM, Shortliffe LD, Williams RD, et al. Alpha-interferon in superficial bladder cancer: a Northern California Oncology Group Study. J Clin Oncol. 1988;6:476–483.

    PubMed  CAS  Google Scholar 

  151. Glashan RW. A randomized controlled study of intravesical alpha-2b-interferon in carcinoma in situ of the bladder. J Urol. 1990;144:658–661.

    PubMed  CAS  Google Scholar 

  152. Boccardo F, Cannata D, Rubagotti A, et al. Prophylaxis of superficial bladder cancer with mitomycin or interferon alfa-2b: results of a multicentric Italian study. J Clin Oncol. 1994;12:7–13.

    PubMed  CAS  Google Scholar 

  153. Jimenez-Cruz JF, Vera-Donoso CD, Leiva O, et al. Intravesical immunoprophylaxis in recurrent superficial bladder cancer (Stage Tl): multicenter trial comparing bacille Calmette-Guerin and interferon-alpha. Urology. 1997;50:529–535.

    Article  PubMed  CAS  Google Scholar 

  154. Stricker P, Pryor K, Nicholson T, et al. Bacillus Calmette-Guerin plus intravesical interferon alpha-2b in patients with superficial bladder cancer. Urology. 1996;48:957–61; discussion 961–962.

    Article  PubMed  CAS  Google Scholar 

  155. Engelmann U, Knopf HJ, Graff J. Interferon-alpha 2b instillation prophylaxis in superficial bladder cancer—a prospective, controlled three-armed trial. Project Group Bochum—Interferon and Superficial Bladder Cancer. Anticancer Drugs. 1992;3:33–37.

    Article  PubMed  Google Scholar 

  156. Raitanen MP, Lukkarinen O. A controlled study of intravesical epirubicin with or without alpha 2b-interferon as prophylaxis for recurrent superficial transitional cell carcinoma of the bladder. Finnish Multicentre Study Group. Br J Urol. 1995;76:697–701.

    Article  PubMed  CAS  Google Scholar 

  157. Slaton JW, Karashima T, Perrotte P, et al. Treatment with low-dose interferon-alpha restores the balance between matrix metalloproteinase-9 and E-cadherin expression in human transitional cell carcinoma of the bladder. Clin Cancer Res. 2001;7:2840–2853.

    PubMed  CAS  Google Scholar 

  158. Slaton JW, Perrotte P, Inoue K, et al. Interferon-alpha-mediated down-regulation of angiogenesis-related genes and therapy of bladder cancer are dependent on optimization of biological dose and schedule. Clin Cancer Res. 1999;5:2726–2734.

    PubMed  CAS  Google Scholar 

  159. Bostrom PJ, Uotila P, Rajala P, et al. Interferon-alpha inhibits cyclooxygenase-1 and stimulates cyclooxygenase-2 expression in bladder cancer cells in vitro. Urol Res. 2001;29:20–24.

    Article  PubMed  CAS  Google Scholar 

  160. Dinney CP, Bielenberg DR, Perrotte P, et al. Inhibition of basic fibroblast growth factor expression, angiogenesis, and growth of human bladder carcinoma in mice by systemic interferon-alpha administration. Cancer Res. 1998;58:808–814.

    PubMed  CAS  Google Scholar 

  161. Giannopoulos A, Adamakis I, Evangelou K, et al. Interferon-a2b reduces neo-microvascular density in the ‘normal’ urothelium adjacent to the tumor after transurethral resection of superficial bladder carcinoma. Onkologie. 2003;26:147–152.

    Article  PubMed  CAS  Google Scholar 

  162. Molto L, Alvarez-Mon M, Carballido J, et al. Intracavitary prophylactic treatment with interferon alpha 2b of patients with superficial bladder cancer is associated with a systemic T-cell activation. Br J Cancer. 1994;70:1247–1251.

    PubMed  CAS  Google Scholar 

  163. Carballido JA, Molto LM, Manzano L, et al. Interferon-alpha-2b enhances the natural killer activity of patients with transitional cell carcinoma of the bladder. Cancer. 1993;72:1743–1748.

    Article  PubMed  CAS  Google Scholar 

  164. Pryor K, Stricker P, Russell P, et al. Antiproliferative effects of bacillus Calmette-Guerin and interferon alpha 2b on human bladder cancer cells in vitro. Cancer Immunol Immunother. 1995;41:309–316.

    Article  PubMed  CAS  Google Scholar 

  165. Borden EC, Groveman DS, Nasu T, et al. Antiproliferative activities of interferons against human bladder carcinoma cell lines in vitro. J Urol. 1984;132:800–803.

    PubMed  CAS  Google Scholar 

  166. Masters G, Brockstein B. Overview of head and neck cancer. Cancer Treat Res. 2003;114:1–13.

    Article  PubMed  Google Scholar 

  167. Whiteside TL. Immunobiology and immunotherapy of head and neck cancer. Curr Oncol Rep. 2001;3:46–55.

    Article  PubMed  CAS  Google Scholar 

  168. Hartmann E, Wollenberg B, Rothenfusser S, et al. Identification and functional analysis of tumor-infiltrating plasmacytoid dendritic cells in head and neck cancer. Cancer Res. 2003;63:6478–6487.

    PubMed  CAS  Google Scholar 

  169. Ikic D, Padovan I, Brodarec I, et al. Application of human leukocyte interferon in patients with tumors of the head and neck. Lancet. 1981;1:1025–1027.

    PubMed  CAS  Google Scholar 

  170. Vlock DR, Johnson J, Myers E, et al. Preliminary trial of non-recombinant interferon alpha in recurrent squamous cell carcinoma of the head and neck. Head Neck. 1991;13:15–21.

    Article  PubMed  CAS  Google Scholar 

  171. Bensmaine ME, Azli N, Domenge C, et al. Phase I–II trial of recombinant interferon alpha-2b with cisplatin and 5-fluorouracil in recurrent and/or metastatic carcinoma of head and neck. Am J Clin Oncol. 1996;19:249–254.

    Article  PubMed  CAS  Google Scholar 

  172. Cascinu S, Fedeli A, Luzi Fedeli S, et al. Cisplatin, 5-fluorouracil and interferon alpha 2b for recurrent or metastatic head and neck cancer. Br J Cancer. 1994;69:392–393.

    PubMed  CAS  Google Scholar 

  173. Huber MH, Shirinian M, Lippman SM, et al. Phase I/II study of cisplatin, 5-fluorouracil and alpha-interferon for recurrent carcinoma of the head and neck. Invest New Drugs. 1994;12:223–229.

    Article  PubMed  CAS  Google Scholar 

  174. Benasso M, Merlano M, Blengio F, et al. Concomitant alpha-interferon and chemotherapy in advanced squamous cell carcinoma of the head and neck. Am J Clin Oncol. 1993;16:465–468.

    Article  PubMed  CAS  Google Scholar 

  175. Hussain M, Benedetti J, Smith RE, et al. Evaluation of 96-hour infusion fluorouracil plus cisplatin in combination with alpha interferon for patients with advanced squamous cell carcinoma of the head and neck: a Southwest Oncology Group study. Cancer. 1995;76:1233–1237.

    Article  PubMed  CAS  Google Scholar 

  176. Schrijvers D, Johnson J, Jiminez U, et al. Phase III trial of modulation of cisplatin/fluorouracil chemotherapy by interferon alfa-2b in patients with recurrent or metastatic head and neck cancer. Head and Neck Interferon Cooperative Study Group. J Clin Oncol. 1998;16:1054–1059.

    PubMed  CAS  Google Scholar 

  177. Schantz SP, Dimery I, Lippman SM, et al. A phase II study of interleukin-2 and interferon-alpha in head and neck cancer. Invest New Drugs. 1992;10:217–223.

    Article  PubMed  CAS  Google Scholar 

  178. Voravud N, Lippman SM, Weber RS, et al. Phase II trial of 13-cis-retinoic acid plus interferon-alpha in recurrent head and neck cancer. Invest New Drugs. 1993;11:57–60.

    Article  PubMed  CAS  Google Scholar 

  179. Lingen MW, Polverini PJ, Bouck NP. Retinoic acid and interferon alpha act synergistically as antiangiogenic and antitumor agents against human head and neck squamous cell carcinoma. Cancer Res. 1998;58:5551–5558.

    PubMed  CAS  Google Scholar 

  180. Lindner DJ, Borden EC, Kalvakolanu DV. Synergistic antitumor effects of a combination of interferons and retinoic acid on human tumor cells in vitro and in vivo. Clin Cancer Res. 1997;3:931–937.

    PubMed  CAS  Google Scholar 

  181. Shin DM, Khuri FR, Murphy B, et al. Combined interferon-alpha, 13-cis-retinoic acid, and alpha-tocopherol in locally advanced head and neck squamous cell carcinoma: novel bioadjuvant phase II trial. J Clin Oncol. 2001;19:3010–3017.

    PubMed  CAS  Google Scholar 

  182. Vlock DR, Andersen J, Kalish LA, et al. Phase II trial of interferon-alpha in locally recurrent or metastatic squamous cell carcinoma of the head and neck: immunological and clinical correlates. J Immunother Emphasis Tumor Immunol. 1996;19:433–442.

    PubMed  CAS  Google Scholar 

  183. King WW, Lam PK, Li AK. Anti-proliferative activity of interferon-alpha on human squamous carcinoma of tongue cell lines. Cancer Lett. 1994;85:55–58.

    Article  PubMed  CAS  Google Scholar 

  184. Lam PK, To EW, Chan ES, et al. In vitro inhibition of head and neck cancer-cell growth by human recombinant interferon-alpha and 13-cis retinoic acid. Br J Biomed Sci. 2001;58:226–229.

    PubMed  CAS  Google Scholar 

  185. Maniar HS, Desai SA, Chiplunkar SV, et al. Modulation of tumour associated antigen expressed on human squamous cell carcinoma cell lines by recombinant interferon-alpha. Eur J Cancer B Oral Oncol. 1993;29B:57–61.

    Article  PubMed  CAS  Google Scholar 

  186. Riedel F, Gotte K, Bergler W, et al. Expression of basic fibroblast growth factor protein and its down-regulation by interferons in head and neck cancer. Head Neck. 2000;22:183–189.

    Article  PubMed  CAS  Google Scholar 

  187. Jones DH, Bleehen NM, Slater AJ, et al. Human lymphoblastoid interferon in the treatment of small cell lung cancer. Br J Cancer. 1983;47:361–366.

    PubMed  CAS  Google Scholar 

  188. Mattson K, Niiranen A, Pyrhonen S, et al. Natural interferon alpha as maintenance therapy for small cell lung cancer. Eur J Cancer. 1992;28A:1387–391.

    Article  PubMed  CAS  Google Scholar 

  189. Kelly K, Crowley JJ, Bunn PA, Jr., et al. Role of recombinant interferon alfa-2a maintenance in patients with limited-stage small-cell lung cancer responding to concurrent chemoradiation: a Southwest Oncology Group study. J Clin Oncol. 1995;13:2924–2930.

    PubMed  CAS  Google Scholar 

  190. Ruotsalainen T, Halme M, Isokangas OP, et al. Interferon-alpha and 13-cis-retinoic acid as maintenance therapy after high-dose combination chemotherapy with growth factor support for small cell lung cancer—a feasibility study. Anticancer Drugs. 2000;11:101–108.

    Article  PubMed  CAS  Google Scholar 

  191. Prior C, Oroszy S, Oberaigner W, et al. Adjunctive interferon-alpha-2c in stage IIIB/IV small-cell lung cancer: a phase III trial. Eur Respir J. 1997;10:392–396.

    Article  PubMed  CAS  Google Scholar 

  192. Zarogoulidis K, Ziogas E, Papagiannis A, et al. Interferon alpha-2a and combined chemotherapy as first line treatment in SCLC patients: a randomized trial. Lung Cancer. 1996;15:197–205.

    Article  PubMed  CAS  Google Scholar 

  193. Olesen BK, Ernst P, Nissen MH, et al. Recombinant interferon A (IFL-rA) therapy of small cell and squamous cell carcinoma of the lung. A phase II study. Eur J Cancer Clin Oncol. 1987;23:987–989.

    Article  PubMed  CAS  Google Scholar 

  194. Niiranen A, Holsti LR, Cantell K, et al. Natural interferon-alpha alone and in combination with conventional therapies in non-small cell lung cancer. A pilot study. Acta Oncol. 1990;29:927–930.

    Article  PubMed  CAS  Google Scholar 

  195. Carmichael J, Fergusson RJ, Wolf CR, et al. Augmentation of cytotoxicity of chemotherapy by human alpha-interferons in human non-small cell lung cancer xenografts. Cancer Res. 1986;46:4916–4920.

    PubMed  CAS  Google Scholar 

  196. Von Hoff DD. In vitro data supporting interferon plus cytotoxic agent combinations. Semin Oncol. 1991;18:58–61.

    Google Scholar 

  197. Bowman A, Fergusson RJ, Allan SG, et al. Potentiation of cisplatin by alpha-interferon in advanced non-small cell lung cancer (NSCLC): a phase II study. Ann Oncol. 1990;1:351–353.

    PubMed  CAS  Google Scholar 

  198. Rosell R, Carles J, Ariza A, et al. A phase II study of days 1 and 8 cisplatin and recombinant alpha-2B interferon in advanced non-small cell lung cancer. Cancer. 1991;67:2448–2453.

    Article  PubMed  CAS  Google Scholar 

  199. Kataja V, Yap A. Combination of cisplatin and interferon-alpha 2a (Roferon-A) in patients with non-small cell lung cancer (NSCLC). An open phase II multicentre study. Eur J Cancer. 1995;31A:35–40.

    PubMed  CAS  Google Scholar 

  200. Mandanas R, Einhom LH, Wheeler B, et al. Carboplatin (CBDCA) plus alpha interferon in metastatic non-small cell lung cancer. A Hoosier Oncology Group phase II trial. Am J Clin Oncol. 1993;16:519–521.

    Article  PubMed  CAS  Google Scholar 

  201. Athanasiadis I, Kies MS, Miller M, et al. Phase II study of all-trans-retinoic acid and alpha-interferon in patients with advanced non-small cell lung cancer. Clin Cancer Res. 1995;1:973–979.

    PubMed  CAS  Google Scholar 

  202. Arnold A, Ayoub J, Douglas L, et al. Phase II trial of 13-cis-retinoic acid plus interferon alpha in non-small-cell lung cancer. The National Cancer Institute of Canada Clinical Trials Group. J Natl Cancer Inst. 1994;86:306–309.

    Article  PubMed  CAS  Google Scholar 

  203. Ardizzoni A, Rosso R, Salvati F, et al. Combination chemotherapy and interferon alpha 2b in the treatment of advanced non-small-cell lung cancer. The Italian Lung Cancer Task Force (FONICAP). Am J Clin Oncol. 1991;14:120–123.

    Article  PubMed  CAS  Google Scholar 

  204. Ardizzoni A, Addamo GF, Baldini E, et al. Mitomycin-ifosfamide-cisplatinum (MIP) vs MIP-interferon vs cisplatinum-carboplatin in metastatic non-small-cell lung cancer: a FONICAP randomized phase II study. Italian Lung Cancer Task Force. Br J Cancer. 1995;71:115–119.

    PubMed  CAS  Google Scholar 

  205. Silva RR, Bascioni R, Rossini S, et al. A phase II study of mitomycin C, vindesine and cisplatin combined with alpha interferon in advanced non-small cell lung cancer. Tumori. 1996;82:68–71.

    PubMed  CAS  Google Scholar 

  206. Hasturk S, Kurt B, Kocabas A, et al. Combination of chemotherapy and recombinant interferon-alpha in advanced non-small cell lung cancer. Cancer Lett. 1997;112:17–22.

    Article  PubMed  CAS  Google Scholar 

  207. Ardizzoni A, Salvati F, Rosso R, et al. Combination of chemotherapy and recombinant alpha-interferon in advanced non-small cell lung cancer. Multicentric Randomized FONICAP Trial Report. The Italian Lung Cancer Task Force. Cancer. 1993;72:2929–2935.

    Article  PubMed  CAS  Google Scholar 

  208. Halme M, Maasilta PK, Pyrhonen SO, et al. Interferons combined with chemotherapy in the treatment of stage III–IV non-small cell lung cancer—a randomized study. Eur J Cancer. 1994;30A:11–15.

    Article  PubMed  CAS  Google Scholar 

  209. Shin DM, Fidler IJ, Bucana CD, et al. Superior antiproliferative effects mediated by interferon-alpha entrapped in liposomes against a newly established human lung cancer cell line. J Biol Response Mod. 1990;9:355–360.

    PubMed  CAS  Google Scholar 

  210. Langdon SP, Rabiasz GJ, Anderson L, et al. Characterization, and properties of a small cell lung cancer cell line and xenograft WX322 with marked sensitivity to alpha-interferon. Br J Cancer. 1991;63:909–915.

    PubMed  CAS  Google Scholar 

  211. Bepler G, Carney DN, Nau MM, et al. Additive and differential biological activity of alpha-interferon A, difluoromethylornithine, and their combination on established human lung cancer cell lines. Cancer Res. 1986;46:3413–3419.

    PubMed  CAS  Google Scholar 

  212. Winters AL, Leach MF, Horton EJ, et al. Depressed interferon synthesis in skin fibroblasts from lung cancer patients. J Interferon Res. 1985;5:465–470.

    PubMed  CAS  Google Scholar 

  213. Sibbitt WL, Jr., Bankhurst AD, Jumonville AJ, et al. Defects in natural killer cell activity and interferon response in human lung carcinoma and malignant melanoma. Cancer Res. 1984;44:852–856.

    PubMed  Google Scholar 

  214. Nissen MH, Plesner T, Larsen JK, et al. Enhanced expression in vivo of HLA-ABC antigens and beta 2-microglobulin on human lymphoid cells induced by human interferon-alpha in patients with lung cancer. Enhanced expression of class I major histocompatibility antigens prior to treatment. Clin Exp Immunol. 1985;59:327–335.

    PubMed  CAS  Google Scholar 

  215. Hokland P, Hokland M, Olesen BK, et al. Effect of recombinant alpha interferon on NK and ADCC function in lung cancer patients: results from a phase II trial. J Interferon Res. 1984;4:561–569.

    PubMed  CAS  Google Scholar 

  216. Kirkwood JM, Bender C, Agarwala S, et al. Mechanisms and management of toxicities associated with high-dose interferon alfa-2b therapy. J Clin Oncol. 2002;20:3703–3718.

    Article  PubMed  CAS  Google Scholar 

  217. Cole BF, Gelber RD, Kirkwood JM, et al. Quality-of-life-adjusted survival analysis of interferon alfa-2b adjuvant treatment of high-risk rejected cutaneous melanoma: an Eastern Cooperative Oncology Group study. J Clin Oncol. 1996;14:2666–2673.

    PubMed  CAS  Google Scholar 

  218. Kilbridge KL, Cole BF, Kirkwood JM, et al. Quality-of-life-adjusted survival analysis of high-dose adjuvant interferon alpha-2b for high-risk melanoma patients using intergroup clinical trial data. J Clin Oncol. 2002;20:1311–1318.

    Article  PubMed  CAS  Google Scholar 

  219. Glue P, Fang JW, Rouzier-Panis R, et al. Pegylated interferon-alpha2b: pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy data. Hepatitis C Intervention Therapy Group. Clin Pharmacol Ther. 2000;68:556–567.

    Article  PubMed  CAS  Google Scholar 

  220. Eggermont AM, Keilholz U, Testori A, et al. The EORTC melanoma group translational research program on prognostic factors and ultrastaging in association with the adjuvant therapy trials in stage II and stage III melanoma. European Organization for Research and Treatment of Cancer. Ann Surg Oncol. 2001;8:38S–40S.

    Article  PubMed  CAS  Google Scholar 

  221. Horton HM, Anderson D, Hernandez P, et al. A gene therapy for cancer using intramuscular injection of plasmid DNA encoding interferon alpha. Proc Natl Acad Sci USA. 1999;96:1553–1558.

    Article  PubMed  CAS  Google Scholar 

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Moschos, S., Varanasi, S., Kirkwood, J.M. (2005). Interferons in the Treatment of Solid Tumors. In: Platanias, L.C. (eds) Cytokines and Cancer. Cancer Treatment and Research, vol 126. Springer, Boston, MA. https://doi.org/10.1007/0-387-24361-5_9

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