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A phase I trial of intrapleural recombinant human interferon α (rHuIFNα2b) in patients with malignant pleural effusions

  • Original Papers
  • Clinical Oncology
  • Published:
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Abstract

The use of intrapleural sclerosing agents to control reaccumulation of pleural fluid in patients with malignant effusions has been widely investigated. A phase I trial of intrapleural recombinant human interferon α (rHuIFNα2b) was initiated to determine the toxicity and maximal tolerated dose in this group of patients. rHuIFNα2b was instilled as a single dose following chest tube (15/16) or percutaneous (1/16) drainage of cytologically proven malignant effusions. Doses of rHuIFNα2b were escalated from 25×106 to 200×106 U/m2 in cohorts of three to four patients. Toxicity was mild to moderate, and included chills, fever and chest pain, and resembled that produced by systemic administration of rHuIFNα2b. Dose-limiting toxicity occurred at 200×106 U/m2 and consisted of hepatic enzyme elevations and renal failure. Partial control of the effusions was noted in two patients, with two additional patients having stable disease. Phase II trials of rHuIFNα2b should utilize up to 150×106 U/m2 for intrapleural instillation.

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Abbreviations

IFN:

interferon

MPE:

malignant pleural effusions

References

  • Cascinu S, Isidor PP, Fedeli A, Fedeli SL, Raspugli M, Rossi A, Ugolini M, Catalano G (1991) Experience with intrapleural natural beta interferon in the treatment of malignant pleural effusions. Tumori 77:237–238

    PubMed  Google Scholar 

  • Chernow B, Sahn SA (1977) Carcinomatous involvement of the pleura. Am J Med 63:695–702

    PubMed  Google Scholar 

  • Creagan ET, Ahmann DL, Green SJ, Long HJ, Rubin J, Schutt AJ, Dziewanowski ZE (1984) Phase II study of recombinant leukocyte A interferon (rIFNαA) in disseminated malignant melanoma. Cancer 54:2844–2849

    PubMed  Google Scholar 

  • Creagan ET, Ahmann DL, Frytak S, Long HJ, Itri LM (1986) Recombinant leukocyte A interferon (rIFNα2A) in the treatment of disseminated malignant melanoma: analysis of complete and long term responding patients. Cancer 58:2576–2578

    PubMed  Google Scholar 

  • Fish EN, Banerjee K, Stebbing N (1983) Human leukocyte interferon subtypes have different antiproliferative and antiviral activities on human cells. Biochem Biophys Res Commun 112:537–546

    PubMed  Google Scholar 

  • Hausheer FH, Jarbro JW (1985) Diagnosis and treatment of malignant pleural effusions. Semin Oncol 12:54–75

    PubMed  Google Scholar 

  • Jereb B, Us-Krasovec M, Cervek J, Soos E (1987) Intrapleural application of human leukocyte interferon (HLI) in breast cancer patients with ipsilateral pleural carcinomatosis. J Interferon Res 7:357–363

    PubMed  Google Scholar 

  • Kirwood JM, Ernstoff M (1986) Potential applications of the interferons in oncology: lessons drawn from studies of human melanoma. Semin Oncol 13:48–56

    Google Scholar 

  • Li DJ, Wang YR, Tan XP, Wang HZ, Yao XD, Ba DN (1990) A new approach to the treatment of malignant effusion. Chin Med J 103:998–1002

    PubMed  Google Scholar 

  • Markowitz A, Thielvoldt D, Yeamans A, Rubenstein E, Escalante C, Friemann C, Hunter J, Gutterman J (1992) Beneficial effects of intracavitary interferon-α2b (IFN): a phase I study of patients with ascites or pleural effusion. Proc Am Soc Clin Oncol 11:258

    Google Scholar 

  • Martini N, Brains MS, Beatti EJ (1975) Indications for pleurectomy in malignant effusions. Cancer 35:734–738

    PubMed  Google Scholar 

  • O'Connell MJ, Colgan JP, Oken MM, Ritts RE, Kay NE (1986) Clinical trial of recombinant leukocyte A interferon as initial therapy for favorable histology non-Hogkin's lymphomas and chronic lymphocytic leukemia. An Eastern Cooperative Oncology Group pilot study. J Clin Oncol 4:128–136

    PubMed  Google Scholar 

  • Pass HI (1989) Treatment of malignant pleural effusions and pericardial effusions. In: DeVita VT, Hellman S, Rosenberg SA (eds) Cancer, principles and practice of oncology, 3rd edn. Lippincott, Philadelphia, p 2320

    Google Scholar 

  • Quesada JR, Reuben J, Manning JT, Hersh EM, Gutterman JU (1984) Alpha-interferon for induction of remission in hairy cell leukemia. N Engl J Med 310:15–18

    PubMed  Google Scholar 

  • Queseda JR, Rios A, Swanson D, Trown P, Gutterman JU (1985) Anti-tumor activity of recombinant-derived interferon α in metastatic renal cell carcinoma. J Clin Oncol 3:1522–1528

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Rosenberg SA, Longo DL, Lotze MT (1989) Principles and applications of biologic therapy. In: DeVita VT, Hellman S, Rosenberg SA (eds) Cancer, principles and practice of oncology, 3rd edn. Lippincott, Philadelphia, pp 328–332

    Google Scholar 

  • Rosso R, Rimoldi R, Salvati F, DePalma M, Cinquegrana A, Nicolo G, Ardizzoni A, Fusco U, Capaccio A, Centofanti R, Neri M, Cruciani AR, Maisto L (1988) Intrapleural natural beta interferon in the treatment of malignant pleural effusions. Oncology 45:253–256

    PubMed  Google Scholar 

  • Ruckdeschel JC, Moores D, Lee JY, Einhorn LH, Mandelbaum I, Koeller J, Weiss GR, Losada M, Keller JH (1991) Intrapleural therapy for malignant pleural effusions. A randomized comparison of bleomycin and tetracycline. Chest 100:1528–35

    PubMed  Google Scholar 

  • Schultz RM, Papamatheakis JD, Chirigos MA (1977) Interferon: an inducer of macrophage activation by polyanions. Science 197:674–676

    PubMed  Google Scholar 

  • Shalaby MR, Svedersky LP, McKay PA, Finkle BS, Palladino MA (1985) In vivo augmentation of natural killer activity by combined treatment with recombinant gamma interferon and interleukin-2. J Interferon Res 5:571–581

    PubMed  Google Scholar 

  • Simon PL, Farrar JJ, Dind PD (1978) Biochemical relationship between murine immune interferon and a killer cell helper factor. J Immunol 122:127–132

    Google Scholar 

  • Talpaz M, Kantarjian HM, Kurzrock R, Trujillo JM, Gutterman JU (1991) Interferon-alpha produces sustained cytogenetic responses in chronic myelocytic leukemia. Ann Intern Med 114:532–538

    PubMed  Google Scholar 

  • West WH, Tauer KW, Yannelli JR, Marshall GD, Orr DW, Thurman GB, Oldham RK (1987) Constant-infusion recombinant interleukin-2 in adoptive immunotherapy of advanced cancer. N Engl Med 316:898–905

    Google Scholar 

  • Yasumoto K, Ogura T (1991) Intrapleural application of recombinant interleukin-2 in patients with malignant pleurisy due to lung cancer. A multi-institutional cooperative study. Biotherapy 3:345–49

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology and Medical Oncology, Cleveland Clinic Foundation, 9500 Euclid Avenue, 44195, Cleveland, Ohio, USA

    A. Bhatia, G. T. Budd, S. Murthy & R. M. Bukowski

  2. Experimental Therapeutics Program, Cleveland Clinic Foundation Cancer Center, Ohio, USA

    D. McLain, P. Herzog & R. M. Bukowski

  3. Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, 9500 Euclid Avenue, 44195, Cleveland, Ohio, USA

    T. W. Rice & T. J. Kirby

Authors
  1. A. Bhatia
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  2. T. W. Rice
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  3. D. McLain
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  4. P. Herzog
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  5. G. T. Budd
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  6. S. Murthy
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  7. T. J. Kirby
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  8. R. M. Bukowski
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Supported in part by a grant from the Schering Corporation, Kenilworth, N.J.

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Bhatia, A., Rice, T.W., McLain, D. et al. A phase I trial of intrapleural recombinant human interferon α (rHuIFNα2b) in patients with malignant pleural effusions. J Cancer Res Clin Oncol 120, 169–172 (1994). https://doi.org/10.1007/BF01202197

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  • DOI: https://doi.org/10.1007/BF01202197

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