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Interferon alfa-2b/melphalan/prednisone in previously untreated patients with multiple myeloma: a phase I–II trial

  • Papers Presented at a Symposium on Interferons in Oncology, Budapest, 26th August, 1986
  • Published:
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Summary

Interferon alfa-2b (Intron A; Schering Plough) has been shown to be active in advanced previously treated multiple myeloma (MM). Recent in vitro evidence has suggested synergy between cytotoxic agents and interferon alfa-2b. This phase I–II protocol was initiated to study interferon alfa-2b in combination with melphalan and prednisone. Groups of five patients received interferon alfa-2b twice-weekly for two weeks at dose levels of 0.5, 1.0, 2.0, 5.0 and 10.0×106 IU/m2. During week 2, melphalan (9 mg/m2) and prednisone (40 mg/m2) were administered concurrently with interferon alfa-2b followed by a rest period during nadir myelosuppression, the cycles being repeated every 28 days. Thirty patients were entered of whom 21 were Stage III, 3 Stage II and 6 Stage I. Median nadir WBC/mm3 and platelets/mm3 at the various dose levels are given in the table.

Serious adverse reactions while on study included myocardial infarction, renal failure and leukopenia-related sepsis. Early response information is available. Twenty-six patients are evaluable for response. Seven have had progressive disease and 19 (69%) a partial response, the median duration was 11+ months. Interferon alfa-2b does not appear to antagonize melphalan/prednisone effectiveness and may be additive or synergistic. Full evaluation of this combination will be undertaken in randomized controlled trials which are now underway.

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References

  1. Bergsagel DE, Phil D, Pruzanski W: Treatment of plasma cell myeloma with cytotoxic agents. Arch Intern Med 135:172–176, 1975

    Google Scholar 

  2. Bergsagel DE, Phil D, Cowan DH: Plasma cell myeloma: response of melphalan resistant patients to high dose intermittent cyclophosphamide. Can Med Assoc J 107:851–855, 1972

    Google Scholar 

  3. Salmon SE, Haut A, Bonnet JD: Alternating combination chemotherapy and levamisole improves survival in multiple myeloma: a Southwest Oncology Group study. J Clin Oncol 1:453–461, 1983

    Google Scholar 

  4. Bergsagel D: Progress in the treatment of plasma cell myeloma. J Clin Oncol 1:510–512, 1983

    Google Scholar 

  5. Case DC Jr, Lee BJ, Clarkson BD: Improved survival times in multiple myeloma treated with melphalan, prednisone, cyclophosphamide, vincristine, BCNU: M-2 protocol. Am J Med 63:897–903, 1977

    Google Scholar 

  6. Alberts DS, Durie BG, Salmon SE: Doxorubicin/BCNU chemotherapy for multiple myeloma in relapse. Lancet 1:926–928, 1976

    Google Scholar 

  7. Costanzi JJ, Cooper MR, Scarffe JH: Phase II study of recombinant alpha-2 interferon in resistant myeloma. J Clin Oncol 3:654–659, 1985

    Google Scholar 

  8. Quesada JR, Alexanian R, Gutterman JU: Induction of remission and restoration of serum immunoglobulins in multiple myeloma with recombinant DNA derived interferon. Blood 64 (Suppl 1):183a, 1984

    Google Scholar 

  9. Mellstedt H, Ahre A, Bjorkhom M: Interferon therapy of patients with multiple myeloma. In WD Terry and SA Rosenberg (eds): Elsevier-North Holland Inc., New York, 1982, pp 387–391

  10. Tan YH, Inoue M: Enhancement of actinomycin-D and cis-diamminedichloroplatinum (II) induced killing of human fibroblasts by human beta-interferon. Cancer Res 43:5484–5488, 1983

    Google Scholar 

  11. Aapro MS, Salmon SE, Alberts DS: Schedule dependent synergism of vinblastine and cloned leukocyte interferon A. Stem Cells 1:303–304, 1981

    Google Scholar 

  12. Tozawa M, Kidowaki T, Terufusa T: Combination therapy of interferon and cyclophosphamide on murine neuroblastoma. J Jpn Soc Cancer Ther 17:613, 1982

    Google Scholar 

  13. Namka M, Yammato S, Tamako H: Potentiation of the cytotoxic effects of various anticancer drugs by interferon on human neoplastic cells (HeLa) in culture. Gan To Kagaku Ryoho 10:1308–1312, 1983

    Google Scholar 

  14. Balkwill FR, Moodie EM: Positive interactions between human interferon and cyclophosphamide or Adriamycin in a human tumor model system. Cancer Res 44:904–908, 1984

    Google Scholar 

  15. Clark RH, Dmitrov NV, Axelson JA: Leucocyte interferon as a biological modification in lymphoproliferative disease. Blood 62 (Suppl 1):188a, 1983

    Google Scholar 

  16. Ferraresi R, Rudnick S, Bonnem EM: Enhanced response to chemotherapy after treatment with DNA alpha-2 interferon. Blood 62 (Suppl 1):212a, 1983

    Google Scholar 

  17. Chronic Leukemia-Myeloma Task Force. National Cancer Institute. Proposed guidelines for protocol studies II. Plasma cell myeloma. Cancer Chemother Rep Part 3, 1(1):17–39, 1968

    Google Scholar 

  18. Alberts DS, Peng YM, Fisher B: Minimal melphalan systemic availability. A potential cause for failure of adjuvant breast cancer. Proc ASCO 3:38, 1984

    Google Scholar 

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Authors and Affiliations

  1. Bowman-Gray School of Medicine, Wake Forest University, Winston-Salem, NC, USA

    M. Robert Cooper

  2. University of Washington, Seattle, USA

    Alexander Fefer & John Thompson

  3. Maine Medical Center, Portland, ME, USA

    Delvyn C. Case Jr

  4. University of Southern California, Los Angeles, LA, USA

    Raymond Kempf

  5. Georgetown University, Washington, DC, USA

    Ronald Sacher & John Neefe

  6. Louisiana State University, New Orleans, LA, USA

    John Bickers

  7. Christie Hospital, Manchester, UK

    J. Howard Scarffe

  8. Schering Corporation, Kenilworth, NJ, USA

    Robert J. Spiegel & Eric M. Bonnem

Authors
  1. M. Robert Cooper
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  2. Alexander Fefer
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  3. John Thompson
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  4. Delvyn C. Case Jr
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  5. Raymond Kempf
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  6. Ronald Sacher
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  7. John Neefe
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  8. John Bickers
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  9. J. Howard Scarffe
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  10. Robert J. Spiegel
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  11. Eric M. Bonnem
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Additional information

This paper originally appeared in Cancer Treatment Reports, 70, 473–476 (1986) and is reproduced by kind permission of the authors and publisher (Ed.).

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Cooper, M.R., Fefer, A., Thompson, J. et al. Interferon alfa-2b/melphalan/prednisone in previously untreated patients with multiple myeloma: a phase I–II trial. Invest New Drugs 5 (Suppl 4), S41–S46 (1987). https://doi.org/10.1007/BF00207262

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  • DOI: https://doi.org/10.1007/BF00207262

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