Skip to main content
SpringerLink
Log in

Interferon-α in Malignant and Viral Diseases

A Review

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Summary

In the 35 years since the discovery of interferon, significant biological activity has been described for interferon-α (IFNα) in various cancers, paticularly haematological malignancies such as hairy cell leukaemia and chronic myelogenous leukaemia. Except for localised therapy in bladder and ovarian cancer, activity against most solid tumours has been disappointing. Other notable exceptions include Kaposi’s sarcoma, renal cell carcinoma and malignant melanoma, tumours known to be susceptible to immunological attack.

More recently, broad spectrum antiviral activity has been demonstrated for both recombinant and naturally occurring IFNα. Hepatitis C is responsive to IFNα in about 40% of patients, but long term remissions are rare. In contrast, long term suppression of hepatitis B is common following IFNα therapy. Both diseases respond in a dose proportional fashion, with daily doses of 5 million units (MU) significantly more effective than lower doses. The mechanism of action in viral diseases involves the expression of unique antiviral proteins such as endonuclease and 2′-5′-oligoadenylate synthetase which enhance the destruction of viral RNA. General cellular protein synthesis is also inhibited, including cytochrome P450 enzymes. This forms the basis for potential drug interactions, with IFNα slowing the clearance of highly metabolised drugs such as theophylline. As an antitumour agent, the mechanism of action of IFNα is unclear, particularly in haematological cancers. In melanoma and renal cell carcinoma, antitumour effects may be mediated by augmented immune responses including activation of natural killer lymphocytes and enhanced expression of cell surface antigens (e.g. MHC I and II). Conversely, antibody formation to recombinant IFNα may result in a loss of activity. This has been observed in both renal cell cancer and hepatitis B and C.

The elimination half-life of IFNα is short, 4 to 5 hours, but biological activity extends for 2 to 3 days after administration, which facilitates daily or thrice weekly administration. Clearance of IFNα is mediated by catabolism in the renal tubules; no intact drug is excreted in the urine.

It is probable that the antiviral indications of IFNα will expand as the agent is more clearly recognised as a primary endogenous defence against various viral conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abdi EA, McPheron TA, Tan Y. Combination of interferon, carboxamide (DTIC) and cimetidine for advanced malignant melanoma. Journal of Biological Response Modifiers 5: 423–427, 1986

    PubMed  CAS  Google Scholar 

  • Adams F, Quesada JR, Gutterman JU. Neuropsychiatric manifestations of human leukocyte interferon therapy in patients with cancer. Journal of the American Medical Association 252: 938–941, 1984

    Article  PubMed  CAS  Google Scholar 

  • Ahre A, Bjorkholm M, Osterborg A, Brenning G, Gahrton G, et al. High doses of natural α-interferon (α-IFN) in the treatment of multiple myeloma — a pilot study from the Myeloma Group of Central Sweden (MGCS). European Journal of Haematology 41: 123–130, 1988

    Article  PubMed  CAS  Google Scholar 

  • Alimena G, Morra E, Lazzarino M, Liberati A, Montefusco E, et al. Interferon alpha-2b as therapy for Ph1-positive chronic myelogenous leukemia: a study of 82 patients treated with intermittent or daily administration. Blood 72: 642, 1988

    PubMed  CAS  Google Scholar 

  • Alter HJ. Transfusion-associated non-A, non-B hepatitis: the first decade. In Zuckerman (Ed.) Viral hepatitis and liver disease, pp. 537–542, Alan R. Liss, New York, 1988

    Google Scholar 

  • Antonelli G, Currenti M, Tutrriziani O, Dianzani F. Neutralizing antibodies to interferon-α: relative frequency in patients treated with different interferon preparations. Journal of Infectious Diseases 163: 882–885, 1991

    Article  PubMed  CAS  Google Scholar 

  • Arima T, Nagashima H, Shimomura H, Takamizawa A, Tsuji T, et al. Treatment of chronic non-A, non-B hepatitis with human beta-interferon. In Zuckerman (Ed.) Viral hepatitis and liver disease, pp. 898–901, Alan R. Liss, New York, 1988

    Google Scholar 

  • Averbuch SD, Austin HA, III, Sherwin SA, Antonovych T, Bunn PA. Acute interstitial nephritis with the nephrotic syndrome following recombinant leukocyte A interferon therapy for mycosis fungoides. New England Journal of Medicine 310: 32–35, 1984

    Article  PubMed  CAS  Google Scholar 

  • Balkiwill FR, Moodie EM. Positive interactions between human interferon and cyclophosphamide or adriamycin in a human tumour model system. Cancer Research 44: 904–908, 1984

    Google Scholar 

  • Beasley RP, Hwang L-Y. Epidemiology of hepatocellular carcinoma. In Vyas et al. (Eds) Viral hepatitis and liver disease, pp. 209–224, Grune & Stratton, Orlando, Florida, 1984

    Google Scholar 

  • Berek JS, Hacker NF, Lichtenstein A, Jung T, Spina C, et al. Intraperitoneal recombinant α-interferon for ‘salvage’ immunotherapy in Stage III epithelial ovarian cancer. A Gynecologic Oncology Group study. Cancer Research 45: 4447–4453, 1985

    PubMed  CAS  Google Scholar 

  • Berens ME, Saito T, Welander CE, Modest EJ. Antitumour activity of new anthracycline analogues in combination with interferon alfa. Cancer Chemotherapy and Pharmacology 19: 301, 1987

    Article  PubMed  CAS  Google Scholar 

  • Bergsagel DE, Haas RH, Messner HA. Interferon alpha 2 in treatment of chronic granulocytic leukemia. Seminars in Oncology 13: 29, 1986

    PubMed  CAS  Google Scholar 

  • Berneman ZN, Gastl G, Gangji D, Van Camp B, Jochmans K et al. Treatment of hairy cell leukemia with recombinant alfa-2-interferon. European Journal of Cancer and Clinical Oncology 27: 987–991, 1986

    Article  Google Scholar 

  • Bernman E, Heller G, Kempin S. Incidence of response and long-term follow-up in patients with hairy cell leukemia treated with recombinant interferon alfa 2a. Blood 75: 839–842, 1990

    Google Scholar 

  • Billard C, Ferbus D, Sigaux F, Castaigne S, Degos L, et al. Action of interferon-alpha on hairy cell leukemia: expression of specific receptors and (2′-5′) oligo (A) synthetase in tumour cells from sensitive and resistant patients. Leukemia Research 12: 11, 1988

    Article  PubMed  CAS  Google Scholar 

  • Billard C, Sigaux F, Castaigne S, Valensi F, Flandrin G, et al. Treatment of hairy cell leukemia with recombinant alpha interferon: II. In vivo down-regulation of alpha interferon receptors on tumour cells. Blood 67: 821, 1986

    PubMed  CAS  Google Scholar 

  • Bino T, Edery H, Gertler A, Rosenberg H. Involvement of the kidney in catabolism of human leukocyte interferon. Journal of General Virology 59: 39–45, 1982

    Article  PubMed  CAS  Google Scholar 

  • Blalock JE, Smith EM. Human leukocyte interferon: potent endorphin-like opioid activity. Biochemical and Biophysical Research Communications 101: 472–478, 1981

    Article  PubMed  CAS  Google Scholar 

  • Blalock JE, Stanton JD. Common pathways of interferon and hormonal action. Nature 283: 406–408, 1980

    Article  PubMed  CAS  Google Scholar 

  • Bocci V, Muscettola M, Grasso G, Paulesu L, Pessina GP, et al. The lymphatic route. 1. Albumin and hyaluronidase modify the normal distribution of interferon in lymph and plasma. Experientia 42: 432–433, 1986

    Article  PubMed  CAS  Google Scholar 

  • Bocci V, Pacini A, Muscettola M, Paulesu L, Pessina GP, et al. Renal filtration, absorption and catabolism of human alpha interferon. Journal of Interferon Research 1: 347–352, 1981

    Article  PubMed  CAS  Google Scholar 

  • Bocci V, Pacini A, Muscettola M, Pessing GP, Paulesu L. The kidney is the main site of interferon catabolism. Journal of Interferon Research 2: 309–314, 1982

    Article  PubMed  CAS  Google Scholar 

  • Boyer CM, Dawson DV, Neal SE, Winchell LF, Leslie DS, et al. Differential induction by interferons of major histocompatibility complex-encoded and non-major histocompatibility complex-encoded antigens in human breast and ovarian carcinoma cell lines. Cancer Research 49: 2928–2934, 1989

    PubMed  CAS  Google Scholar 

  • Brunda MJ, Tarnowski D, Davatelis V,. Effect of combinations of recombinant interferon alpha and interleukin-2 on tumor metastases and cytotoxic cell function. In Lotzova & Herberman (Eds) Natural immunity, cancer and biological response modification, pp. 235–241, Karger, Basel, 1986

    Google Scholar 

  • Bunn Jr PA, Ihde DC, Foon KA. The role of recombinant interferon alfa-2a in the therapy of cutaneous T-cell lymphomas. Cancer 57: 1689–1695, 1986

    Article  PubMed  Google Scholar 

  • Bunney MH. Viral warts: their biology and treatment, pp. 5–9, Oxford University Press, New York, 1982

    Google Scholar 

  • Buzaid AC, Robertone A, Kisala C, Salmon SE. Phase II study of interferon alfa-2α, recombinant (Roferon-A) in metastatic renal cell carcinoma. Journal of Clinical Oncology 5: 1083–1089, 1987

    PubMed  CAS  Google Scholar 

  • Cantell K, Hervonen S, Morgensen KE. Human leukocyte interferon production, purification, and animal experiments. In Waymouth C (Ed.) In vitro, pp. 35–38, Baltimore Tissue Culture Association, Baltimore, 1975

    Google Scholar 

  • Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, et al. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244: 359–362, 1989

    Article  PubMed  CAS  Google Scholar 

  • Choo YC, Seto WH, Hsu C, Merigan TC, Tan YH, et al. Cervical intraepithelial neoplasia treated by perilesional injection of interferon. British Journal of Obstetrics and Gynaecology 93: 372–379, 1986

    PubMed  CAS  Google Scholar 

  • Chrisp P, McTavish D. Levamisole/fluorouracil. A review of their pharmacology and adjuvant therapeutic use in colorectal cancer. Drugs & Aging 1: 317–337, 1991

    Article  CAS  Google Scholar 

  • Chun HG, Leyland-Jones B, Cheson BD. Fludarabine phosphate: a synthetic purine antimetabolite with significant activity against lymphoid malignancies. Journal of Clinical Oncology 9: 175–188, 1991

    PubMed  CAS  Google Scholar 

  • Cooper MR, Fefer A, Thompson J, Case DC Jr, Kempf R, et al. Alpha-2 interferon/melphalan/ prednisone in previously untreated patients with multiple myeloma: a phase I-II trial. Cancer Treatment Reports 70: 473–476, 1986

    PubMed  CAS  Google Scholar 

  • Corrado C, Pavlovsky S, Saslasky J, Lein J, Palau V, et al. Randomized trial comparing melphalan-prednisone with or without recombinant alfa 2 interferon (rα2 IFN) in multiple myeloma. Abstract. Proceedings of the American Society of Clinical Oncologists 8: 258, 1989

    Google Scholar 

  • Craig PI, Mehta I, Murray M, McDonald D, Astrom A, et al. Interferon down-regulates the male-specific cytochrome P450IIIA2 in rats. Molecular Pharmacology 38: 313–318, 1990

    PubMed  CAS  Google Scholar 

  • Craig PI, Murray M, Farrell GC. Interferon suppresses the isoform-specific activities of hepatic cytochrome P450 in female rats. Biochemical Pharmacology 43: 908–910, 1992

    Article  PubMed  CAS  Google Scholar 

  • Creagan ET, Ahmann DL, Frytak S, Long HJ, Chang MN, et al. Recombinant leukocyte A interferon (rIFN-alpha A) in the treatment of disseminated malignant melanoma: analysis of complete and long-term responding patients. Cancer 58: 2576, 1986

    Article  PubMed  CAS  Google Scholar 

  • Creagan ET, Ahmann DL, Green SJ, Long HJ, Frytak S, et al. Phase II study of low-dose recombinant leukocyte A interferon in disseminated malignant melanoma. Journal of Clinical Oncology 2: 1002, 1984a

    PubMed  CAS  Google Scholar 

  • Creagan ET, Ahmann DL, Green SJ, Long HJ, Rubin J, et al. Phase II study of recombinant leukocyte A interferon (rIFN-alpha A) in disseminated malignant melanoma. Cancer 54: 2844,1984b

    Article  PubMed  CAS  Google Scholar 

  • Creagan ET, Ahmann DL, Green SJ, Long HJ, Frytak S, et al. Phase II study of leukocyte A interferon (IFN Alfa a) plus cimetidine in disseminated malignant melanoma (DMM). Journal of Clinical Oncology 3: 977, 1985

    PubMed  CAS  Google Scholar 

  • Croghan MK, Booth A, Meyskens FL. A phase I trial of recombinant interferon-alpha and alpha-difluoromethylornithine in metastatic melanoma. Journal of Biological Response Modifiers 7: 409, 1988

    PubMed  CAS  Google Scholar 

  • Dadmarz R, Evans T, Secher D, Marshall N, Cawley JC. Hairy cells possess more interferon receptors than other lymphoid cell types. Leukemia 1: 357, 1987

    PubMed  CAS  Google Scholar 

  • Davis GL, Balart LA, Schiff ER, Lindsay K, Bodenheimer HC, et al. Treatment of chronic hepatitis C with recombinant interferon alfa. A multicenter randomized, controlled trial. New England Journal of Medicine 321: 1501–1506, 1989

    Article  PubMed  CAS  Google Scholar 

  • de Wit R, Schatenkerk JK, Boucher CB, Bakker PJ, Venhof KN, et al. Clinical and virological effects of high-dose recombinant interferon-α in disseminated AIDS-related Kaposi’s sarcoma. Lancet 2: 1214–1217, 1988

    Article  PubMed  Google Scholar 

  • Dhingra K, Talpaz M, Dhingra HM, Ajani JA, Rothberg JM, et al. A phase I trial of recombinant alpha-2a interferon (Roferon-A) with weekly cisplatinum. Investigational New Drugs 9: 37–39, 1991

    PubMed  CAS  Google Scholar 

  • Di Bisceglie AM, Martin P, Kassianides C, Lisker-Melman M, Murray L, et al. Recombinant inteferon alfa therapy for chronic hepatitis C. A randomized, double-blind, placebo-controlled trial. New England Journal of Medicine 321: 1506–1510, 1989

    Article  PubMed  Google Scholar 

  • Diaz MO, Rubin CM, Harden A, Ziemin S, Larson RA, et al. Deletions of interferon genes in acute lymphoblastic leukemia. New England Journal of Medicine 322: 77–82, 1990

    Article  PubMed  CAS  Google Scholar 

  • Diaz MO, Ziemin S, LeBeau MM, Pitha P, Smith SD, et al. Hemozygous deletion of the α-and β1 -interferon genes in human leukemia and derived cell lines. Proceedings of the National Academy of Sciences of the USA 85: 5259–5263, 1988

    Article  PubMed  CAS  Google Scholar 

  • Dickson D. Death halts interferon trials in France. Science 218: 772, 1982

    Article  PubMed  CAS  Google Scholar 

  • Dorr RT, Shipp NG. Effect of interferon, interleukin-2 and tumor necrosis factor on myocardial cell viability and doxorubicin cardiotoxicity in vitro. Immunopharmacology 18: 31–38, 1989

    Article  PubMed  CAS  Google Scholar 

  • Dorval T, Palangie T, Jouve M, Garcia-Giralt E, Israel L, et al. Clinical phase II trial of recombinant DNA interferon (interferon alfa 2b) in patients with metastatic malignant melanoma. Cancer 58: 215, 1986

    PubMed  CAS  Google Scholar 

  • Dukes PP, Izadi P, Ortega JA, Shore NA, Gomperts E. Inhibitory effects of interferon on mouse megakaryocytic progenitor cells in culture. Experimental Hematology 8: 1048–1051, 1980

    PubMed  CAS  Google Scholar 

  • Durie BGM, Clouse L, Braich T, Grimm M, Robertone AB, et al. Interferon alfa-2b-cyclophosphamide combination studies: in vitro and phase I-II clinical results. Seminars in Oncology 13: 84–88, 1986

    PubMed  CAS  Google Scholar 

  • Einhorn N, Ling P, Strander H. Systemic interferon alpha treatment of human condylomata acuminata. Acta Obstetricia et Gynecolica Scandinavica 62: 285–287, 1983

    Article  CAS  Google Scholar 

  • Einhorn S, Blomgren H, Strander H. Interferon and spontaneous cytotoxicity: II. Studies in patients receiving exogenous leukocyte interferon. Acta Medica Scandinavica 204: 477, 1978

    Article  PubMed  CAS  Google Scholar 

  • Einzig AI, Krown SE, Oettgen HF Recombinant leukocyte a interferon (γIFN-α) in renal cell cancer. Abstract. Proceedings of the American Society of Clinical Oncology 4: 54, 1984

    Google Scholar 

  • Elsasser-Beile U, Drews H. Interferon in the treatment of malignant melanoma. Results of clinical studies. Fortschritte der Medizin 105: 401–406, 1987

    PubMed  CAS  Google Scholar 

  • Erikkson B, Oberg K, Alm G, Karlsson A, Lundqvist, et al. Treatment of malignant endocrine pancreatic tumors with human leukocyte interferon. Cancer Treatment Reports 71: 31–37, 1987

    Google Scholar 

  • Ernstoff MS, Fusi S, Kirkwood JM. Parameters of interferon action: I. Immunological effects of whole cell leukocyte interferon in phase I/II trials. Journal of Biological Response Modifiers 2: 528, 1983

    PubMed  CAS  Google Scholar 

  • Eron LJ, Judson F, Tucker S, Prawer S, Mills J, et al. Interferon therapy for condylomata acuminata. New England Journal of Medicine 315: 1059–1064, 1986

    Article  PubMed  CAS  Google Scholar 

  • Figlin RA, Callaghan M, Sarna A. Phase II trial of α (human leukocyte) interferon administered daily in adenocarcinoma of the colon/rectum. Cancer Treatment Reports 67: 1009–1012, 1983

    Google Scholar 

  • Fischl MA, Uttamchandani RB, Resnick L. A phase I study of recombinant human interferons alfa-2a or human lympho-blastoid interferon alf n-1 and concomitant zidovudine in patients with AIDS-related Kaposi’s sarcoma. Journal of Acquired Immune Deficiency Syndromes 4: 1–10, 1991

    PubMed  CAS  Google Scholar 

  • Fisher RI, Coltman Jr CA, Doroshow JH, Rayner AA, Hawkins MJ, et al. Metastatiac renal cancer treated with interleukin-2 and lymphokine-activated killer cells. Annals of Internal Medicine 108: 518–523, 1988

    PubMed  CAS  Google Scholar 

  • Flandrin G, Sigaux F, Sebahoun G, Boufette P. Hairy cell leukemia: clinical presentation and follow-up of 211 patients. Seminars in Oncology (Suppl. 2) 11: 458, 1984

    CAS  Google Scholar 

  • Flodgren P, Borgstrom S, Jonsson PE, Lindström C, Sjögren HO. Metastatic malignant melanoma: regression induced by combined treatment with interferon [huIFN-alpha(le)] and cimetidine. International Journal of Cancer 32: 657, 1983

    Article  CAS  Google Scholar 

  • Foa R, Fiero MT, Lusso P, Bonferroni M, Raspadori D, et al. Effect of alpha-interferon on the immune system of patients with hairy cell leukemia. Leukemia 1: 377, 1987

    PubMed  CAS  Google Scholar 

  • Foon K, Doroshow J, Bonnern E, Fefer A, Graham S, et al. A prospective randomised trial of alpha 2B-interferon/gamma interferon or the combination in advanced metastatic renal cell carcinoma. Journal of Biological Response Modifiers 7: 540–545, 1988

    PubMed  CAS  Google Scholar 

  • Foon KA, Roth MS, Bunn Jr PA. Interferon therapy of non-Hodgkin’s lymphoma. Cancer 59: 601–604, 1987

    Article  PubMed  CAS  Google Scholar 

  • Foon KA, Sherwin SA, Abrams PG, Longo DL, Fer MF, et al. Treatment of advanced non-Hodgkin’s lymphoma with recombinant leukocyte A interferon. New England Journal of Medicine 311: 1148–1152, 1984

    Article  PubMed  CAS  Google Scholar 

  • Fossa SD. Is interferon with or without vinblastine the ‘treatment of choice’ in metastatic renal cell carcinoma? The Norwegian Radium Hospital’s experience 1983–1986. Seminars in Surgical Oncology 4: 178–183, 1988

    Article  PubMed  CAS  Google Scholar 

  • Fung WE. Interferon alpha 2a for treatment of age-related macular degeneration. American Journal of Ophthalmology 112: 349–350, 1991

    PubMed  CAS  Google Scholar 

  • Gale RP, Foon KA. Chronic lymphocytic leukemia: recent advances in biology and treatment. Annals of Internal Medicine 103: 101–120, 1985

    PubMed  CAS  Google Scholar 

  • Geffen JR, Klein RJ, Friedman-Kien AE. Intralesional administration of large doses of human leukocyte interferon for the treatment of condylomata acuminata. Journal of Infectious Diseases 150: 612–615, 1984

    Article  PubMed  CAS  Google Scholar 

  • Giacomini P, Imberti L, Aguzzi A, Fisher FB, Trinchieri G, et al. Immunochemical analysis of the modulation of human melanoma-associated antigens by DNA recombinant immune interferon. Journal of Immunology 135: 2887–2894, 1985

    CAS  Google Scholar 

  • Gibson JR, Harvey SG. Interferon in the treatment of persistent viral warts. British Journal of Dermatology 109: 694–695, 1983

    Google Scholar 

  • Giles FJ, Singer CRJ, Gray AG, Brozovic M, Yong KL, et al. Alpha-interferon therapy for essential thrombocythaemia. Lancet 2: 70–72, 1988

    Article  PubMed  CAS  Google Scholar 

  • Goldstein D, Gockerman J, Krishnan R, Ritchie J, Iso CY, et al. Effects of γ-interferon on the endocrine system: results from a phase I study. Cancer Research 47: 6397–6401, 1987

    PubMed  CAS  Google Scholar 

  • Goldstein D, Laszlo J. Interferon therapy in cancer: from imaginon to interferon. Cancer Research 46: 4315–4329, 1986

    PubMed  CAS  Google Scholar 

  • Golomb HM, Fefer A, Golde DW. Sequential evaluation of alpha 2b interferon treatment in 128 patients with hairy cell leukemia. Seminars in Oncology (Suppl.) 14: 13–17, 1987

    CAS  Google Scholar 

  • Golomb HM, Jacobs A, Fefer A, Ozer H, Thompon J, et al. Alpha-2 interferon therapy of hairy-cell leukemia: a multicenter study of 64 patients. Journal of Clinical Oncology 4: 900, 1986

    PubMed  CAS  Google Scholar 

  • Greenway HT, Cornell RC, Tanner DJ, Peets E, Bordin GM, et al. Treatment of basal cell carcinoma with intralesional interferon. Journal of the American Academy of Dermatology 15: 437–443, 1986

    Article  PubMed  CAS  Google Scholar 

  • Gressler VH, Weinkauff RE, Franklin WA, Golomb HM. Modulation of the expression of major histocompatibility antigens on splenic hairy cells — differential effect upon in vitro treatment with alpha-2b interferon, gamma-interferon, and interleukin-2. Blood 72: 1048, 1988

    PubMed  CAS  Google Scholar 

  • Groopman JE, Gottlieb MS, Goodman J, Itsoyaso RT, Conant MA, et al. Recombinant alpha-2 interferon therapy for Kaposi’s sarcoma associated with the acquired immunodeficiency syndrome. Annals of Internal Medicine 100: 671–676, 1984

    PubMed  CAS  Google Scholar 

  • Groopman JE, Mitsuyasu RT, DeLeo MJ, Oette DH, Golde DW. Effect of recombinant human granulocyte-macrophage colony-stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome. New England Journal of Medicine 317: 593–598, 1987

    Article  PubMed  CAS  Google Scholar 

  • Gutterman JU, Blemeshein GR, Alexanian R, Yap HY, Buzder AU. Leukocyte interferon-induced tumor regression in human metastatic breast cancer, multiple myeloma, and malignant lymphoma. Annals of Internal Medicine 93: 399–406, 1980

    PubMed  CAS  Google Scholar 

  • Hartshorn KL, Vogt MW, Chou TC, Blumberg RS, Byington R, et al. Synergistic inhibition of human immunodeficiency virus in vitro by azidothymidine and recombinant alpha A interferon. Antimicrobial Agents and Chemotherapy 31: 168–172, 1987

    Article  PubMed  CAS  Google Scholar 

  • Hersey P, Hasic E, MacDonald M, Edwards A, Spurting A, et al. Effects of recombinant leukocyte interferon (rIFN-alpha A) on tumour growth and immune responses in patients with metastatic melanoma. British Journal of Cancer 51: 815, 1985

    Article  PubMed  CAS  Google Scholar 

  • Hersh EM, Gutterman JU, Spector S. Impaired in vitro interferon, blastogenic and natural killer cell responses to viral stimulation in acquired immunodeficiency syndrome. Cancer Research 45: 406–410, 1985

    PubMed  CAS  Google Scholar 

  • Higano CS, Raskind W, Durnam D, Messner HA, Smith JT, et al. Alpha interferon (IFN) induces cytogenetic remissions in patients who relapse with chronic myelogenous leukemia (CML) after allogenic bone marrow transplantation (BMT). Abstract. Blood 74: 83a, 1989

    Google Scholar 

  • Hoofnagle JH, Mullen KD, Jones DB, Rustgi V, Bisceglie AD, et al. Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon: a preliminary report. New England Journal of Medicine 315: 1575–1578, 1986

    Article  PubMed  CAS  Google Scholar 

  • Hoofnagle JH, Peters M, Mullen KD, Jones DB, Rustgi V. Randomized, controlled trial of recombinant human α-interferon in patients with chronic hepatitis B. Gastroenterology 95: 1318–1325, 1988

    PubMed  CAS  Google Scholar 

  • Horning SJ, Merigan TC, Krown SE, Gutterman JU, Louie A, et al. Human interferon alpha in malignant lymphoma and Hodgkin’s disease. Cancer 56: 1305–1310, 1985

    Article  PubMed  CAS  Google Scholar 

  • Houghton AN, Thomson TM, Gross D, Oeftgen HF, Old LJ. Surface antigens of melanoma and melanocytes. Specificity of induction of Ia antigens by human gamma-interferon. Journal of Experimental Medicine 160: 255–269, 1984

    CAS  Google Scholar 

  • Hrushesky WJ, Murphy GP. Current status of the therapy of advanced renal carcinoma. Journal of Surgical Oncology 9: 277–288, 1977

    Article  PubMed  CAS  Google Scholar 

  • Iigo M, Sakurai M, Tamura T, Saijo N, Hoshi A, et al. In vivo antitumor activity of multiple injections of recombinant interleukin-2 alone and in combination with three different types of recombinant interferon on various syngeneic murine tumors. Cancer Research 48: 260–264, 1988

    PubMed  CAS  Google Scholar 

  • Jacobs P, LeRoux I, Wood L, Bolding E. Interferon response in B-cell prolymphocytic leukemia. British Journal of Hematology 65: 375–376, 1987

    Article  CAS  Google Scholar 

  • Jacobs SL, Kelsey DK. Antibodies in patients with hairy-cell leukemia receiving alpha-2b interferon. New England Journal of Medicine 315: 1418, 1986

    PubMed  CAS  Google Scholar 

  • Johnston JB, Eisenhauer E, Corbett WEN, Scott JG, Zaentz SD. Efficacy of 2’-deoxycoformycin in hairy-cell leukemia: a study of the National Cancer Institute of Canada Clinical Trials Group. Journal of the National Cancer Institute 80: 765, 1988

    Article  PubMed  CAS  Google Scholar 

  • Jones GJ, Itri LM. Safety and tolerance of recombinant interferon alfa-2a (Roferon-A®) in cancer patients. Cancer 57: 1709–1715, 1986

    Article  PubMed  CAS  Google Scholar 

  • Kameyama K, Tanaka S, Ishida Y, Hearing VJ. Interferons modulate the expression of hormone receptors on the surface of murine melanoma cells. Journal of Clinical Investigation 83: 213–217, 1989

    Article  PubMed  CAS  Google Scholar 

  • Kantarjian H, Keating M, McCredie K, Talpaz M, Gutterman JU. Treatment of advanced stages of Philadelphia-chromosome (Ph)-positive chronic myelogenous leukemia (CML) with alpha interferon (IFN-A) and low-dose cytosine arabinoside (ara-C). Abstract. Blood 7: 235a, 1989a

    Google Scholar 

  • Kantarjian H, Talpaz M, Keating M, McCredie K, Kurzrock R, et al. Therapy of Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia with initial intensive chemotherapy (DOAP) followed by maintenance with human leukocyte alpha interferon. Abstract. Blood 67: 224a, 1986

    Google Scholar 

  • Kantarjian H, Talpaz M, Spinolo J, Kurzrock R, Gutterman JU, et al. High doses of cyclophosphamide, BCNU and etoposide (CBV) induce cytogenetic responses in most patients with advanced stages of Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). Abstract. Blood 74: 2273a, 1989b

    Google Scholar 

  • Kaposi M. Idiopathisches multiples Pigment-Sarkom der Haut. Archives of Dermatological Syphilis 4: 265–273, 1872

    Google Scholar 

  • Kirkwood JM, Ernstoff MS. Potential applications of the interferons in oncology: lessions drawn from studies of human melanoma. Seminars in Oncology (Suppl. 2) 13: 48, 1986

    CAS  Google Scholar 

  • Kirkwood JM, Ernstoff MS. Cutaneous melanoma. In DeVita et al. (Eds), Biologic therapy of cancer, pp. 311–33, JB Lippincott, Baltimore, Maryland, 1991

    Google Scholar 

  • Kirkwood JM, Ernstoff MS, Davis CA, Reiss M, Feraresi R, et al. Comparison of intramuscular and intravenous recombinant alpha-2 interferon in melanoma and other cancers. Annals of Internal Medicine 103: 32, 1985

    PubMed  CAS  Google Scholar 

  • Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1: 431–435, 1981

    Article  PubMed  CAS  Google Scholar 

  • Koretz RL, Stone O, Mousa M, Gitnick GL. Non-A, non-B post transfusion hepatitis — a decade later. Gastroenterology 88: 1251–1254, 1985

    PubMed  CAS  Google Scholar 

  • Kovacs JA, Deyton L, Davey R, Falloon J, Zunich K. Combined zidovudine and interferon-α therapy in patients with Kaposi sarcoma and the acquired immunodeficiency syndrome (AIDS). Annals of Internal Medicine 111: 280–287, 1989

    PubMed  CAS  Google Scholar 

  • Kraut EH, Bouroncle B, Grever MR. Pentostatin in the treatment of advanced hairy cell leukemia. Journal of Clinical Oncology 7: 168, 1989

    PubMed  CAS  Google Scholar 

  • Krigel R, Padavit K, Rudolph A, Bradley E, Konrad M, et al. Renal cell carcinoma: treatment with recombinant interleukin 2 (rIL-2) plus beta interferon (IFN-3). Proceedings of the American Society of Clinical Oncology 8: 186, 1989

    Google Scholar 

  • Krigel RL, Slywotzky CM, Lonberg M. Treatment of epidemic Kaposi’s sarcoma with a combination of interferon alpha 2b and etoposide. Journal of Biological Response Modifiers 7: 359–364, 1988

    PubMed  CAS  Google Scholar 

  • Krown SE, AIDS and Kaposi’s sarcoma: interferons in pathogenesis and treatment. In Gresser (Ed.) Interferon 7, pp. 185–211, Academic Press, London, 1986

    Google Scholar 

  • Krown SE. The role of interferon in the therapy of epidemic Kaposi’s sarcoma. Seminars in Oncology (Suppl.) 14: 27–33, 1987

    CAS  Google Scholar 

  • Krown SE. Kaposi’s sarcoma. In DeVita VT et al. (Eds) Biologic therapy of cancer, pp. 346–353, JB Lippincott, Philadelphia, 1991

    Google Scholar 

  • Krown SE, Einzig AI, Abramson JD, Oettgem HF, et al. Treatment of advanced renal cell cancer (RCC) with recombinant leukocyte A interferon (rIFN-αA). Absract. Proceedings of the American Society of Clinical Oncology 2: 58, 1983

    Google Scholar 

  • Krown SE, Gold JWM, Niedzwiecki D, Bundow D, Flomenberg N, et al. Interferon-α with zidovudine: safety, tolerance, and clinical and virologic effects in patients with Kaposi’s sarcoma associated with the acquired immunodeficiency syndrome (AIDS). Annals of Internal Medicine 112: 812–821, 1990

    PubMed  CAS  Google Scholar 

  • Krown SE, Real FX, Cunningham-Rundles S, Myskowski PL, Kozinere B, et al. Preliminary observations on the effect on recombinant leukocyte A interferon in homosexual men with Kaposi’s sarcoma. New England Journal of Medicine 308: 1071–1076, 1983

    Article  PubMed  CAS  Google Scholar 

  • Kuo G, Choo Q-L, Alter HJ, Gitnick GL, Redeker AG, et al. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 244: 362–364, 1989

    Article  PubMed  CAS  Google Scholar 

  • Kurzrock R, Rhode MF, Quesada J. Recombinant γ interferon induces hypoertriglyceridemia and inhibits post-heparin lipase activity in cancer patients. Journal of Experimental Medicine 164: 1093–1101, 1986

    Article  PubMed  CAS  Google Scholar 

  • Kurzrock R, Talpaz M, Gutterman JU. Interferons-α, β, γ basic principles and preclinical studies. In DeVita et al. (Eds) Biologic therapy of cancer, pp. 247–274, JB Lippincott, Philadelphia, 1991

    Google Scholar 

  • Kurzrock R, Talpaz M, Gutterman JU. Other tumors. In DeVita et al. (Eds) Biologic therapy of cancer, pp. 334–346, JB Lippincott, Philadelphia, 1991

    Google Scholar 

  • Lane HC, Falloon J, Walker RE. Zidovudine in patients with human immunodeficiency virus (HIV) infection and Kaposi’s sarcoma. Annals of Internal Medicine 111: 41–50, 1989

    PubMed  CAS  Google Scholar 

  • Lane HC, Kovacs JA, Feinberg J, Herpin B, Davey V, et al. Antiretroviral effects of interferon-α in AIDS-associated Kaposi’s sarcoma. Lancet 2: 1218–1222, 1988

    Article  PubMed  CAS  Google Scholar 

  • Laurie JA, Moertel CG, Fleming TR, Wieand HS, Leigh JE, et al. Surgical adjuvant therapy of large-bowel carcinoma: an evaluation of levamisole and the combination of levamisole and fluorouracil. Journal of Clinical Oncology 7: 1447–1456, 1989

    PubMed  CAS  Google Scholar 

  • Lazzarino M, Bitale A, Morra E, ((two more authors please??)) et al. Interferon α-2b in the treatment of Philadelphia negative chronic myeloproliferative disorders with excessive thrombocytosis. New Trends in Therapy of Leukemia and Lymphoma 2: 83–88, 1987

    Google Scholar 

  • Leavitt RD, Ratanatharathorn V, Ozer H, Ultmann JE, Portlock C, et al. Alfa-2b interferon in the treatment of Hodgkin’s disease and non-Hodgkin’s lymphoma. Seminars in Oncology 14: 18–23, 1987

    PubMed  CAS  Google Scholar 

  • Lee KH, Talpaz M, Rothberg JM, Murray JL, Papadopoulos N, et al. Concomitant administration of recombinant human interleukin-2 and recombinant interferon α-2A in cancer patients: a phase I study. Journal of Clinical Oncology 7: 1726–1732, 1989

    PubMed  CAS  Google Scholar 

  • Lopez C, Fitzgerald PA, Siegel FP. Severe acquired immune deficiency syndrome in male homosexuals: diminished capacity to make interferon-α in vitro associated with severe opportunistic infections. Journal of Infectious Diseases 148: 962–966, 1983

    Article  PubMed  CAS  Google Scholar 

  • Ludwig H, Linkesch W, Gisslinger H, Fritz E, Sinzininger H, et al. Interferon-alfa corrects thrombocytosis in patients with myeloproliferative disorders. Cancer Immunology Immunotherapy 25: 266–273, 1987

    Article  CAS  Google Scholar 

  • Ma DDF, Arthur CK. Treatment of chronic myeloid leukemia (CML) using alfa-interferon (IFN), and low dose cytosine arabinoside (ara-C). Abstract. Blood 74: 363a, 1989

    Google Scholar 

  • Maheshware RK, Lazo PS, Friedman RM. Enhancement of interferon activity by a membrane glycoprotein related to the thyrotropin receptor. In Khan et al. (Eds) Interferon: properties and clinical uses, pp. (387–396), Leland Fikes Foundation Press of the Wadley Institute of Molecular Medicine, Dallas, 1979

  • Maio M, Gulwani B, Langer JA, Kerbel RS, Duigou GJ, et al. Modulation by interferons of HLA antigen, high molecular weight melanoma-associated antigen, and intercellular adhesion molecule I expression by cultured melanoma cells with different metastatic potential. Cancer Research 49: 2980–2987, 1989

    PubMed  CAS  Google Scholar 

  • Mandelli F, Avvisati G, Amadori S, Boccadoro M, Gernone A, et al. Maintenance treatment with recombinant interferon alfa-2b in patients with multiple myeloma responding to conventional induction chemotherapy. New England Journal of Medicine 322: 1430–1434, 1990

    Article  PubMed  CAS  Google Scholar 

  • Margolis S. Therapy for condyloma acuminatum: a review. Reviews of Infectious Diseases (Suppl.) 4: S829–S836, 1982

    Article  Google Scholar 

  • Markowitz A, Talpaz M, Lee K. Phase I-II study of recombinant interleukin-α2A plus recombinant interferon-α2a in renal cell carcinoma. Proceedings of the American Society of Clinical Oncology 8: 146, 1989

    Google Scholar 

  • Martinelli G, Cavalli F. α-Interferon alone or in combination with chemotherapy in the treatment of malignant melanoma, renal cell carcinoma and other solid tumours. In Veronesi (Ed.) Interferons in oncology, current status and future direction, pp. (33–38), Springer-Verlag, 1987

  • Massaro ER, Borden EC, Hawkins MJ, Wiebe DA, Shrago E. Effects or recombinant interferon-α2 treatment upon lipid concentrations and lipoprotein composition. Journal of Interferon Research 6: 655–662, 1986

    Article  PubMed  CAS  Google Scholar 

  • Maxwell B, Talpaz M, Gutterman JU. Down-regulation of peripheral blood cell interferon receptors in chronic myelogenous leukemia patients undergoing human interferon (HuIFN) therapy. International Journal of Cancer 36: 23–29, 1985

    Article  CAS  Google Scholar 

  • McLeod GR, Thomson DB, Hersey P. Recombinant interferon alfa-2a in advanced malignant melanoma. A phase I-II study in combination with DTIC. International Journal of Cancer (Suppl.) 1: 31, 1987

    Article  CAS  Google Scholar 

  • Medencia R, Slack N. Clinical results of leukocyte interferon-induced tumor regression in resistant human metastatic cancer resistant to chemotherapy and/or radiotherapy-pulse therapy schedule. Cancer Drug Delivery 2: 53–57, 1985

    Article  Google Scholar 

  • Mellstedt H. Treatment of multiple myeloma with natural alpha interferon. Haematological Oncology 6: 187–192, 1988

    Article  CAS  Google Scholar 

  • Meyers JD, Fluornoy N, Sanders JE, McGuffm RW, Newton BA, et al. Prophylactic use of human leukocyte interferon after allogeneic marrow transplantation. Annals of Internal Medicine 107: 809–816, 1987

    PubMed  CAS  Google Scholar 

  • Miller RL, Steis RG, Clark JW, Smith JW, Crum E, et al. Randomized trial of recombinant α2b-interferon with or without indomethacin in patients with metastatic malignant melanoma. Cancer Research 49: 1871–1876, 1989

    PubMed  CAS  Google Scholar 

  • Mitsuyasu RT. Clinical variants and staging of Kaposi’s sarcoma. Seminars in Oncology (Suppl. 3) 14: 13–18, 1987

    PubMed  CAS  Google Scholar 

  • Moller BR, Johannesen P, Osther K, Ulmsteen U, Hastrup J, et al. Treatment of dysplasia of the cervical epithelium with an interferon gel. Obstetrics and Gynecology 62: 625–629, 1983

    PubMed  CAS  Google Scholar 

  • Mongini P, Seremetis S, Blessinger C, Rudich S, Winchester R, et al. Diversity in inhibitory effects of IFN-gamma and IFN-alpha A on the induced DNA synthesis of a hairy cell leukemia B lymphocyte clone reflects the nature of the activating ligand. Blood 72: 1553, 1988

    PubMed  CAS  Google Scholar 

  • Moormeier JA, Golomb HM. Interferon: clinical applications. In DeVita et al. (Eds) Biologic therapy of cancer, pp. 275–289, JB Lippicott, Philadelphia, 1991

    Google Scholar 

  • Moormeier JA, Ratain MJ, Westbrook CA, Vardiman JW, Daly KM, et al. Low-dose interferon alfa-2b in the treatment of hairy cell leukemia. Journal of the National Cancer Institute 81: 1172, 1989

    Article  PubMed  CAS  Google Scholar 

  • Mossman TR, Coffman RL. Th1 and Th2 cells: different patterns of lymphokine secretion lead to different functional properties. Annual Review of Immunology 7: 145–167, 1989

    Article  Google Scholar 

  • Mughal TI, Robinson WA, Thomas MR, Spiegel R. Role of recombinant alpha2 and cimetidine in patients with advanced malignant melanoma. Journal of Cancer Research and Clinical Oncology 114: 108–109, 1988

    Article  PubMed  CAS  Google Scholar 

  • Muss HB. Renal cell carcinoma. In DeVita et al. (Eds) Biologic therapy of cancer, pp. 298–311, JB Lippincott, Philadelphia, 1991

    Google Scholar 

  • Muss HB, Costanzi JJ, Leavitt R, Williams RD, Kempf RA, et al. Recombinant alfa interferon in renal cell carcinoma: a randomized trial of two routes of administration. Journal of Clinical Oncology 5: 286–291, 1987

    PubMed  CAS  Google Scholar 

  • Nachbaur DM, Denz HA, Gastl G, Thaler J, Lechleitner M, et al. Combination effects of human recombinant inteferon (alpha-2-arg, gamma) and cytotoxic agents on colony formation of human melanoma and hypernephroma cell lines. Cancer Letters 44: 49, 1989

    Article  PubMed  CAS  Google Scholar 

  • Nardi M, Cognetti F, Giulia MD, Sternberg C, Lombardi A, et al. Intraperitoneal rα2-interferon (IFN) alternating with cis-platin (DDP) as salvage therapy for minimal residual disease ovarian cancer. Abstract. Proceedings of the American Society of Clinical Oncology 8: 157, 1989

    Google Scholar 

  • Neefe JR, Silgals R, Ayoob M, Schein PS. Minimal activity of recombinant clone A interferon in metastatic colon cancer. Journal of Biological Response Modifiers 3: 366–370, 1984

    PubMed  CAS  Google Scholar 

  • Neidhart J, Gagen M, Kisner R, Tuttle R, Whisnant J. Therapy of renal cancer with low (LD), intermediate (ID), and high (HD) dose regimens of human lymphoblastoid interferon (HBLI; Wellferon®). Absract. Proceedings of the American Society of Clinical Oncology 3: 60, 1984

    Google Scholar 

  • Nicolas JF, Balblanc JC, Frappaz A, Chouvet B, Delcombel M, et al. Treatment of cutaneous T cell lymphoma with intermediate doses of interferon alpha 2a. Dermatologica 179: 34–37, 1989

    Article  PubMed  CAS  Google Scholar 

  • Niederle N, Doberauer C, Kloke O, Osieka R, Schweers C, et al. Treatment of chronic myelogenous leukemia with recombinant interferon alpha (IFN-α2b). Proceedings of the American Society of Clinical Oncology 5: 236, 1986

    Google Scholar 

  • Niloff JM, Knapp RC, Jones G, Schaetzl EM, Bast RC. Recombinant leukocyte α-interferon in advanced ovarian carcinoma. Cancer Treatment Reports 69: 895–896, 1985

    PubMed  CAS  Google Scholar 

  • Oberg K, Alm G, Magnusson A, Lundgvist G, Theodorsson E, et al. Treatment of malignant carcinoid tumors with recombinant interferon alfa-2b: development of neutralizing interferon antibodies and possible loss of antitumor activity. Journal of the National Cancer Inst 81: 531–535, 1989

    Article  CAS  Google Scholar 

  • Ohno R, Kumura K. Treatment of multiple myeloma with recombinant interferon alfa-2a. Cancer 57: 1685–1688, 1986

    Article  PubMed  CAS  Google Scholar 

  • Oken MM, Kyle RA, Greipp PR, Kay NE, Tsiatis A, et al. Complete remission (CR) induction with VMBCP + interferon (rIFNα2) in multiple myeloma: 3-year follow-up. Abstract. Proceedings of the American Society of Clinical Oncology 8: 272, 1989

    Google Scholar 

  • Oken MM, Kyle RA, Kay NE, Kay NE, Greipp PR, O’Connell MJ. A phase II trial of interferon alpha2 (rIFNa2) in the treatment of resistant multiple myeloma (MM). Abstract. Proceedings of the American Society of Clinical Oncology 4: 215, 1985

    Google Scholar 

  • Olsen EA, Rosen ST, Vollmer RT, Variakojis D, Roenigk Jr HH, et al. Interferon alfa-2a in the treatment of cutaneous T cell lymphoma. Journal of the American Academy of Dermatology 20: 395–407, 1989

    Article  PubMed  CAS  Google Scholar 

  • Osterborg A, Bjorkholm M, Gahrton G. Melphalan/prednisone (MP) therapy vs melphalan/prednisone + human α-interferon (MP/IFN) therapy in patients with multiple myeloma, Stage II and III. A randomized study from the Myeloma Group of Central Sweden (MGCS). An interimistic report. Abstract. Annual Meeting of the Swedish Medical Society, Stockholm, Sweden, December 2–4, p. 169, 1987

  • Ozer H, Golomb HM, Zimmerman H, Spiegel RJ, et al. Cost-benefit analysis of interferon alfa-2b in the treatment of hairy cell leukemia. Journal of the National Cancer Institute 81: 594, 1989

    Article  PubMed  CAS  Google Scholar 

  • Pan L, Guyre PM. Individual and combined tumoricidal effects of dexamethasone and interferons on human leukocyte cell lines. Cancer Research 48: 567–571, 1988

    PubMed  CAS  Google Scholar 

  • Pangalis GA, Griva E. Recombinant alfa-2b-interferon therapy in untreated, stages A and B chronic lymphocytic leukemia. A preliminary report. Cancer 61: 869–872, 1988

    Article  PubMed  CAS  Google Scholar 

  • Pappas SC, Hoofnagle JH, Young N, Huang M-T, Thomas PE, et al. Treatment of chronic non-A, non-B hepatitis with acyclovir pilot study. Journal of Medical Virology 15: 1–9, 1985

    Article  PubMed  CAS  Google Scholar 

  • Parkinson A, Lasker J, Kramer MJ, Huang M-T, Thomas PE, et al. Effects of three recombinant human leukocyte interferons on drug metabolism in mice. Drug Metabolism and Disposition 10: 579–585, 1982

    PubMed  CAS  Google Scholar 

  • Patel NP, Livengood RW. Renal cell cancer: natural history and results of treatment. Journal of Urology 119: 722–726, 1977

    Google Scholar 

  • Pazin GJ, Ho M, Haverkos HW, Armstrong JA, Breinig MC, et al. Effects of interferon-alpha on human warts. Journal of Interferon Research 2: 235–243, 1982

    Article  PubMed  CAS  Google Scholar 

  • Perrillo RP, Schiff ER, Davis GL, Bodenheimer HC, Lindsay K, et al. A randomized, controlled trial of interferon alfa-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. New England Journal of Medicine 323: 295–301, 1990

    Article  PubMed  CAS  Google Scholar 

  • Pestka S, Maeda S, Chiang T-R, Costello L, Rehberg E, et al. Cloning and expression of human interferons in microorganisms. Texas Reports on Biology and Medicine 41: 198–208, 1982

    CAS  Google Scholar 

  • Petrelli N, Douglass Jr HO, Herrera L, Russell D, Stablein D, et al. The modulation of fluorouracil with leucovorin in metastatic colorectal carcinoma: a prospective randomized phase III trial. Journal of Clinical Oncology 7: 1419–1426, 1989

    PubMed  CAS  Google Scholar 

  • Piro LD, Carrera CJ, Carson DA, Beutler E. Lasting remissions in hairy-cell leukemia induced by a single infusion of 2-chlorodeoxyadenosine. New England Journal of Medicine 322: 1117–1121, 1990

    Article  PubMed  CAS  Google Scholar 

  • Pizzocaro G, Piva L, DiFronzo G, Giongo A, Cozzoli A, et al. Adjuvant medroxyprogesterone acetate to radical nephrectomy in renal cancer: 5-year results of a prospective randomized study. Journal of Urology 138: 1379–1381, 1987

    PubMed  CAS  Google Scholar 

  • Pralle H, Zwingers T, Boedewadt S, Bross K, Dörken B, et al. A prospective multicenter trial with human recombinant alpha-2c-interferon in hairy cell leukemia before and after splenectomy. Leukemia 1: 337, 1987

    PubMed  CAS  Google Scholar 

  • Quesada JR, Alexanian R, Hawkins M, Barlogie B, Borden E, al. Treatment of multiple myeloma with recombinant α-interferon. Blood 67: 275–278, 1986c

    PubMed  CAS  Google Scholar 

  • Quesada JR, Hawkins M, Horning S, Alexanian R, Borden E, et al. Collaborative phase I-II study of recombinant DNA-produced leukocyte interferon (clone A) in metastatic breast cancer, malignant lymphoma, and multiple myeloma. American Journal of Medicine 77: 427–432, 1984

    Article  PubMed  CAS  Google Scholar 

  • Quesada JR, Hersh EM, Manning J, Reuben J, Keating M, et al. Treatment of hairy cell leukemia with recombinant alpha interferon. Blood 68: 493–497, 1986a

    PubMed  CAS  Google Scholar 

  • Quesada JR, Itri L, Gutterman JU. Alpha interferons in hairy cell leukemia: a five year follow-up of 100 patients. Abstract. Journal of Interferon Research 7: 678, 1987a

    Google Scholar 

  • Quesada JR, Lepe-Zuniga JL, Gutterman JU. Mid-term observations on the efficacy of alpha-interferon in hairy cell leukemia and status of the interferon system of patients in remission. Leukemia 1: 317, 1987b

    PubMed  CAS  Google Scholar 

  • Quesada JR, Reuben J, Manning JT, Hersh EM, Gutterman JU. Alpha interferon for induction of remission in hairy-cell leukemia. New England Journal of Medicine 310: 15, 1984

    Article  PubMed  CAS  Google Scholar 

  • Quesada JR, Rios A, Swanson D, Trown P, Gutterman JU. Antitumor activity of recombinant-derived interferon alpha in metastatic renal cell carcinoma. Journal of Clinical Oncology 3: 1522–1528, 1985

    PubMed  CAS  Google Scholar 

  • Quesada JR, Talpaz M, Rios A, Kurzrock R, Gutterman JU. Clinical toxicity of interferons in cancer patients: a review. Journal of Clinical Oncology 4: 234–243, 1986b

    PubMed  CAS  Google Scholar 

  • Radwanski E, Perentesis G, Oden E, Jacobs S, Oden E, Affrime M, et al. Pharmacokinetics of INF α-2b in healthy volunteers. Journal of Clinical Pharmacology 27: 432–435, 1987

    PubMed  CAS  Google Scholar 

  • Ramani P, Balkwill FR. Human interferons inhibit experimental metastases of a human melanoma cell line in nude mice. British Journal of Cancer 58: 350, 1988

    Article  PubMed  CAS  Google Scholar 

  • Ratain MJ, Golomb HM, Bardawil RG, Vardiman J, Westbrook C, et al. Durability of responses to interferon alfa-2b in advanced hairy cell leukemia. Blood 69: 872, 1987

    PubMed  CAS  Google Scholar 

  • Ratain MJ, Golomb HM, Vardiman JW, Westbrook CA, Barker C, et al. Relapse after interferon alfa-2b therapy for hairy cell leukemia. Analysis of prognostic variables. Journal of Clinical Oncology 6: 1714, 1988

    PubMed  CAS  Google Scholar 

  • 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. Journal of Clinical Oncology 4: 544–551, 1986

    PubMed  CAS  Google Scholar 

  • Realdi G, Alberti A, Rugge M, Rigoli AM, Tremolada F, et al. Long-term follow-up of acute and chronic non-A, non-B post-transfusion hepatitis: evidence of progression to liver cirrhosis. Gut 23: 270–275, 1982

    Article  PubMed  CAS  Google Scholar 

  • Redman BG, Flaherty L, Chou T-H, al-Katib A, Kraut M, et al. A phase I trial of recombinant interleukin-2 combined with recombinant interferon-gamma in patients with cancer. Journal of Clinical Oncology 8: 1269–1276, 1990

    PubMed  CAS  Google Scholar 

  • Robinson WA, Mughal TI, Thomas MR, Johnson M, Spiegel RJ. Treatment of metastatic malignant melanoma with recombinant interferon alpha 2. Immunobiology 172: 275, 1986

    Article  PubMed  CAS  Google Scholar 

  • Rohantiner AZ, Prior PF, Burton AL, Smith AT, Balkwill FR, et al. Central nervous system toxicity of interferon. British Journal of Cancer 47: 419–422, 1983

    Article  Google Scholar 

  • Rosa FM, Cochet MM, Fellous M. Interferon and major histocompatibility complex genes: a model to analyse eukaryotic gene regulation? In Gresser (Ed.) Interferon 7, pp. 47–87, Academic Press, New York, 1986

    Google Scholar 

  • Rosa F, Fellous M. The effect of 7-interferon on MHC antigens. Immunology Today 5: 261–262, 1984

    Article  Google Scholar 

  • Rosenblum MG, Gutterman JU. Synergistic antiproliferative activity of leukocyte interferon in combination with α-difluoromethylornithine against human cells in culture. Cancer Research 44: 2339–2340, 1984

    PubMed  CAS  Google Scholar 

  • Rosenblum MG, Maxwell BL, Talpaz M, Kelleher PJ, McCredie KB, et al. In vivo sensitivity and resistance of chronic myelogenous leukemia cells to α-interferon: correlation with receptor binding and induction of 2′,5′-oligoadenylate synthetase. Cancer Research 49: 4848–4852, 1989

    Google Scholar 

  • Rozman C, Montserrat E, Vinolas N, Urbano-Ispizua A, Ribera José et al. Recombinant α2-interferon in the treatment of B chronic lymphocytic leukemia in early stages. Blood 71: 1295–1298, 1988

    PubMed  CAS  Google Scholar 

  • Rupprecht RM, O’Brien L, Rosas D, Andersen J, Recombinant human interferon α A/D (F Hu IFN-αA/D) enhances the antiretroviral effect of 3′arido-3′-deoxythymidine (AZT) in mice. Proceedings of the American Association of Cancer Research 28: 456, 1987

    Google Scholar 

  • Safai B, Good RA. Kaposi’s sarcoma: a review and recent developments. Cancer 31: 2–12, 1981

    CAS  Google Scholar 

  • Saito T, Berens ME, Welander EC. Characterization of the indirect antitumor effect of gamma-interferon using ascites-associated macrophages in a human tumor clonogenic assay. Cancer Research 47: 673, 1987

    PubMed  CAS  Google Scholar 

  • Salmon SE, Durie BG, Young L, Liu RM, Trown PW, et al. Effects of cloned human leukocyte interferons in the human tumor stem cell assay. Journal of Clinical Oncology 1: 217, 1983

    PubMed  CAS  Google Scholar 

  • Samuels BL, Golomb HM, Brownstein BH. In vitro induction of proteins by alpha-interferon in hairy cell leukemia. Cancer Research 46: 4151, 1986

    PubMed  CAS  Google Scholar 

  • Sarosy GA, Brown TD, Von Hoff DD, Spiegel RJ, Golando JP, et al. Phase I study of α2-interferon plus doxorubicin in patients with solid tumors. Cancer Research 46: 5368–5371, 1986

    PubMed  CAS  Google Scholar 

  • Schmitz-Drager BJ, Ebert T. Intravesical treatment of superficial bladder carcinoma with interferons. World Journal of Urology 3: 218–223, 1986

    Article  Google Scholar 

  • Schnall SF, Davis C, Kirkwood JM, Ziyadeh T, Kirkwood JM, Pasquale D, et al. Treatment of metastatic renal cell carcinoma (RCC) with intramuscular (IM) recombinant alpha A (IFN, Hoffman-La Roche). Abstract. Proceedings of the American Society of Clinical Oncology 5: 227, 1986

    Google Scholar 

  • Schüller J, Czejka M, Miksche M, Fogl U, Schernthaner G. Influence of interferon α 2b (IFN) ± leucovorin (LV) on pharmacokinetics (PK) of 5-fluorouracil. Abstract. Proceedings of the American Society of Clinical Oncology 10: 98, 1991

    Google Scholar 

  • Scott GM, Csonka GW. Effect of injections of small doses of human fibroblast interferon into genital warts: a pilot study. British Journal of Venereal Diseases 55: 442–445, 1979

    PubMed  CAS  Google Scholar 

  • Sertoli MR, Bernengo MG, Ardizzoni A, Brunetti I, Falcone A, et al. Phase II trial of recombinant alpha-2b interferon in the treatment of metastatic skin melanoma. Oncology 46: 96, 1989

    Article  PubMed  CAS  Google Scholar 

  • Shepherd FA, Evans WK, Garvey B, Read SE, Klein M, et al. Combination chemotherapy and α-interferori in the treatment of Kaposi’s sarcoma associated with acquired immune deficiency syndrome. Canadian Medical Association Journal 139: 635–639, 1988

    PubMed  CAS  Google Scholar 

  • Siegel JP. Effects of interferon-γ on the activation of human T lymphocytes. Cell Immunology 111: 461–472, 1988

    Article  CAS  Google Scholar 

  • Silgals RM, Ahlgren JD, Neefe JR. A phase II trial of high-dose intravenous interferon α-2 in advanced colorectal cancer. Cancer 56: 2257–2261, 1984

    Article  Google Scholar 

  • Silverberg E, Boring CC, Squires TS. Cancer Statistics 1990. CA: A Journal for Clinicians 40: 9–26, 1990

    Article  CAS  Google Scholar 

  • Singh G, Renton KW. Interferon-mediated depression of cyto-chrome P-450-dependent drug biotransformation. Molecular Pharmacology 20: 681–684, 1981

    PubMed  CAS  Google Scholar 

  • Skotnicki AB, Wolska-Smolen T, Blicharski J, Zdunczyk A, Sasiadek U, et al. Human recombinant interferon-alpha-2 in the treatment of patients with hairy cell Jeukemia. Cancer Detection and Prevention 12: 511–522, 1988

    PubMed  CAS  Google Scholar 

  • Smedley H, Katrak M, Sikora K, Wheeler T. Neurologic effects of recombinant human interferon. British Medical Journal 286: 262–264, 1983

    Article  PubMed  CAS  Google Scholar 

  • Smith DB, Scarffe JH, Wagstaff J, Johnston RJ. Phase II trial of rDNA alfa 2b interferon in patients with malignant carcinoid tumor. Cancer Treatment Reports 71: 1265–1266, 1987

    PubMed  CAS  Google Scholar 

  • Smith JW, II, Longo DL, Urba WJ, Bernhardt L, Wills RJ. Prolonged, continuous treatment of hairy cell leukemia patients with recombinant interferon-α2a. Blood 78: 1664–1671, 1991

    PubMed  Google Scholar 

  • Smith RA, Norris F, Palmer D, Bernhardt L, Wills RJ, et al. Distribution of alpha interferon in serum and cerebrospinal fluid after systemic administration. Clinical Pharmacology and Therapeutics 37: 85–88, 1985

    Article  PubMed  CAS  Google Scholar 

  • Spiegel RJ. Additional indications for interferon therapy: basal cell carcinoma, carcinoid, and chronic active hepatitis. Seminars in Oncology 15: 41–45, 1988

    PubMed  CAS  Google Scholar 

  • Steiner A, Wolf C, Penhamberger H. Comparison of the effects of three different treatment regimens of recombinant interferons (r-IFN alpha, r-IFN gamma, and r-IFN alpha plus cimetidine in disseminated malignant melanoma. Journal of Cancer Research and Clinical Oncology 113: 459–465, 1987

    Article  PubMed  CAS  Google Scholar 

  • Steis RG, Smith JW, II, Urba WJ, Clark JW, Itri LM, et al. Resistance to recombinant interferon alfa-2a in hairy-cell leukemia associated with neutralizing anti-interferon antibodies. New England Journal of Medicine 318: 1409, 1988

    Article  PubMed  CAS  Google Scholar 

  • Stokes P, Lopez WC, Balart LA. Effects of short-term corticosteroid therapy in patients with chronic non-A, non-B hepatitis (NANB). Abstract. Gastroenterology 92: 1783, 1987

    Google Scholar 

  • Swarzinger I, Bettelheim P, Chott A, et al. Recombinant alpha-interferon for progressive hairy cell leukemia: a study in previously untreated splenectomized patients. Wiener Klinische Wochenschrift 100: 47–52, 1988

    Google Scholar 

  • Talpaz M, Kantarjian H, Kurzrock R, Gutterman JU. Chronic myelogenous leukemia and myeloproliferative disorders. In DeVita et al. (Eds) Biologic therapy of cancer, pp. 289–298, JB Lippincott, Philadelphia, 1991

    Google Scholar 

  • Talpaz M, Kantarjian HM, McCredie KB, Trujillo JM, Keating MJ, et al. (1986) Hematologic remission and cytogenetic improvement induced by recombinant human interferon alpha in chronic myelogenous leukemia. New England Journal of Medicine 314: 1065–1069, 1986

    Article  PubMed  CAS  Google Scholar 

  • Talpaz M, Mavligit G, Keating M, Walters RS, Gutterman JU. Human leukocyte interferon to control thrombocytosis in chronic myelogenous leukemia. Annals of Internal Medicine 99: 789–792, 1983a

    PubMed  CAS  Google Scholar 

  • Talpaz M, McCredie KB, Mavligit GM, Gutterman J. Leukocyte interferon-induced myeloid cytoreduction in chronic myelogenous leukemia. Blood 62: 689, 1983b

    PubMed  CAS  Google Scholar 

  • Talpaz M, Rosenblum M, Kurzrock R, Reuben J, Kantarjian H, et al. Clinical and laboratory changes induced by alpha interferon in chronic lymphocytic leukemia — a pilot study. American Journal of Hematology 24: 341–350, 1987

    Article  PubMed  CAS  Google Scholar 

  • Torti FM. Treatment of metastatic renal cell carcinoma. Recent results. Cancer Research 85: 123–142, 1983

    CAS  Google Scholar 

  • Torti FM, Shortliffe LD, Williams RD, Pitts WC, Kempson RL, et al. Alpha-interferon in superficial bladder cancer. Journal of Clinical Oncology 6: 476–483, 1988

    PubMed  CAS  Google Scholar 

  • Tovey MG, Rochette-Egly C, Castagna M. Effect of interferon on concentrations of cyclic nucleotides in cultured cells. Proceedings of the National Academy of Sciencce USA 76: 3890–3893, 1979

    Article  CAS  Google Scholar 

  • Umeda T, Niijima N. Phase II study of alpha interferon on renal cell carcinoma: summary of three collaboratorive trials. Cancer 58: 1231–1235, 1986

    Article  PubMed  CAS  Google Scholar 

  • Vance JC, Bart BJ, Hansen RC, Reichman RC, McEwen C, et al. Intralesional recombinant alpha-2 interferon for the treatment of patients with condyloma acuminatum or verruca plantaris. Archives of Dermatology 122: 272–277, 1986

    Article  PubMed  CAS  Google Scholar 

  • Volberding PA, Mitsuyasu RT, Golando JP, Spiegel RJ. Treatment of Kaposi’s sarcoma with interferon alfa-2b (Intron A®). Cancer 59: 620–625, 1987

    Article  PubMed  CAS  Google Scholar 

  • von Roemeling R, Rabatin JT, Fraley EE, Hrushesky WJM. Progressive metastatic renal cell carcinoma controlled by continuous 5-fluoro-2-deoxyuridine infusion. Journal of Urology 139: 259–262, 1988

    Google Scholar 

  • von Wussow P, Block B, Hartmann F, Deicher H. Intralesional interferon-alpha therapy in advanced malignant melanoma. Cancer 61: 1071–1074, 1988

    Article  Google Scholar 

  • Von Wussow P, Freund M, Dahle S, et al. Immunogenicity of different types of interferons in the treatment of hairy-cell leukemia. New England Journal of Medicine 319: 226, 1988

    Google Scholar 

  • Wadler S, Lyver A, Goldman M, et al. Therapy with 5-fluorouracil and recombinant interferon-alpha in refractory gastrointestinal malignancies. Abstract. Proceedings of the American Society of Clinical Oncology 8: 99, 1988

    Google Scholar 

  • Wadler S, Schwartz EL, Goldman M, Lyver A, Rader M, et al. Fluorouracil and recombinant alfa-2a-interferon: an active regimen against advanced colorectal carcinoma. Journal of Clinical Oncology 7: 1769–1775, 1989

    PubMed  CAS  Google Scholar 

  • Walsh C, Speyer JL, Wernz J, Hochster H, Grossberg H, et al. Phase I study of the combination of alpha-2 interferon and cisplatinum. Journal of Biological Response Modifiers 8: 11, 1989

    PubMed  CAS  Google Scholar 

  • Weber JS, Jay G, Tanaka K, Rosenberg SA. Immunotherapy of a murine tumor with interleukin-2; increased sensitivity after MHC class I gene transfection. Journal of Experimental Medicine 166: 1716–1733, 1987

    Article  PubMed  CAS  Google Scholar 

  • Weissburg JI, Andres LL, Smith CI, Weick S, Nichols JE, et al. Survival in chronic hepatitis B: an analysis of 379 patients. Annals of Internal Medicine 101: 613–616, 1984

    Google Scholar 

  • Welander CE. Interferon in the treatment of ovarian cancer. Seminars in Oncology 15: 26–29, 1988

    PubMed  CAS  Google Scholar 

  • Wells RJ, Weck PK, Baehner RL, Krivit W, Raney RB, et al. Interferon-α-n 1 in children with recurrent acute lymphocytic leukemia: a phase I study of pharmacokinetics and tolerance. Journal of Interferon Research 8: 309–318, 1988

    Article  PubMed  CAS  Google Scholar 

  • Willemse PHB, deVries EGE, Oosterhuis BE, Aalders JG, Bouma J, et al. Intraperitoneal human r-IFN 2αb in patients with stage III minimal residual ovarian cancer. Abstract. Proceedings of the American Society of Clinical Oncology 8: 155, 1989

    Google Scholar 

  • Williams RD. Intravesical interferon alfa in the treatment of superficial bladder cancer. Seminars in Oncology 15 (Suppl. 5): 10–17, 1988

    PubMed  CAS  Google Scholar 

  • Williams RD, Sarosdy M, Catalona W, Chodak G, Vogelzang N, et al. Randomized trial of high vs low dose intravesical interferon alpha 2B treatment of bladder carcinoma in situ. Abstract. Journal of Clinical Oncology 7: 121, 1988

    Google Scholar 

  • Williams SJ, Baird-Lambert JA, Farrell GC. Inhibition of theophylline metabolism by interferon. Lancet 2: 939–941, 1987

    Article  PubMed  CAS  Google Scholar 

  • Wills RJ, Dennis S, Spiegel HE, Gibson DM, Nadler PI, et al. Interferon kinetics and adverse reactions after intravenous, intramuscular, and subcutaneous injection. Clinical Pharmacology and Therapeutics 35: 722–727, 1984

    Article  PubMed  CAS  Google Scholar 

  • Wills RJ, Spiegel HE. Continuous intravenous infusion pharmacokinetics of interferon to patients with leukemia. Journal of Clinical Pharmacology 25: 616–619, 1985

    PubMed  CAS  Google Scholar 

  • Witter FR, Woods AS, Griffin MD, Mith CR, Nadler P, et al. Effects of prednisone, aspirin, and acetaminophen on an in vivo biologic response to interferon in human. Clinical Pharmacology and Therapeutics 44: 239–243, 1988

    Article  PubMed  CAS  Google Scholar 

  • Worman CP, Catovsky D, Cawley JC, Bevan PC, Bottomley JM, et al. The U.K. experience with human lymphoblastoid interferon in HCL: a report of the first 50 cases. Leukemia 1: 320, 1987

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. 1515 N. Campbell Avenue, Tucson, Arizona, AZ 85724, USA

    Robert T. Dorr

Authors
  1. Robert T. Dorr
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dorr, R.T. Interferon-α in Malignant and Viral Diseases. Drugs 45, 177–211 (1993). https://doi.org/10.2165/00003495-199345020-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-199345020-00003

Keywords

Search

Navigation