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Treatment of Bendamustine and Prednisone in patients with newly diagnosed multiple myeloma results in superior complete response rate, prolonged time to treatment failure and improved quality of life compared to treatment with Melphalan and Prednisone—a randomized phase III study of the East German Study Group of Hematology and Oncology (OSHO)

Journal of Cancer Research and Clinical Oncology volume 132, pages 205–212 (2006)Cite this article

Abstract

Purpose: This randomized phase III study compared bendamustine and prednisone (BP) to standard melphalan and prednisone (MP) treatment in previously untreated patients with multiple Myeloma (MM). Patients and Methods: To be included, patients had to have histologically and cytologically proven stage II with progressive diseases or stage III MM. They were randomly assigned to receive BP (n=68) or MP (n=63). The primary endpoint was the time to treatment failure (TTF). Secondary endpoints included survival, remission rate, toxicity and quality of life. Results: The overall response rate was 75% in the BP and 70% in the MP group. A significantly higher number of patients treated with BP achieved a complete remission than did patients receiving MP (32 vs. 13%; P=0.007), and the maximum response was achieved more rapidly in patients treated with BP compared to those receiving MP (6.8 vs. 8.7 cycles; P<0.02). TTF and remission duration were significantly longer in the BP group. Patients receiving BP had higher QoL scores and reported pain less frequently than patients receiving MP. Conclusion: BP is superior to MP with respect to complete remission rate, TTF, cycles needed to achieve maximum remission and quality of life and should be considered the new standard in first-line treatment of MM patients not eligible for transplantation.

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References

  • Alberts DS, Chang SY, Chen HS, Evans TL, Moon TE (1979) Oral melphalan kinetics. Clin Pharmacol Ther 26(6):737–745

    PubMed  CAS  Google Scholar 

  • Alexanian R, Dimopoulos M (1994) The treatment of multiple myeloma. N Engl J Med 330(7):484–489

    PubMed  Article  CAS  Google Scholar 

  • Alexanian R, Bonnet J, Gehan E, Haut A, Hewlett J, Lane M et al (1972) Combination chemotherapy for multiple myeloma. Cancer 30(2):382–389

    PubMed  Article  CAS  Google Scholar 

  • Anger G, Hesse P, Baufeld H (1969) Treatment of multiple myeloma with a new cytostatic agent: gamma-l-methyl-5-bis-(beta-chlorethyl)-amino-benzimidazolyl-(2)-butyric acid hydrochloride. DMW 94(48):2495–2500

    CAS  Google Scholar 

  • Anger G, Fink R, Fleischer J, Hesse P, Krug K, Raderecht C et al (1975) Vergleichsuntersuchungen zwischen Cytostasan und Cyclophosphamid bei der chronischen Lymphadenose, dem Plasmozytom, der Lymphogranulomatose und dem Bronchialkarzinom. Dt Gesundh -Wesen 30(27):1280–1285

    Google Scholar 

  • Attal G, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF et al (1996) A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. New Engl J Med 335(2):91–97

    PubMed  Article  CAS  Google Scholar 

  • Barlogie B, Jagannath S, Desikan KR, Mattox S, Vesole D, Siegel D et al (1999) Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood 93(1):55–65

    PubMed  CAS  Google Scholar 

  • Bensinger WI, Buckner D, Gahrton G (1997) Allogeneic stem cell transplantation for multiple myeloma. Hematol Oncol Clin North Am 11(1):147–157

    PubMed  Article  CAS  Google Scholar 

  • Bergsagel DE, Sprague CC, Austin C, Griffith KM (1962) Evaluation of new chemotherapeutic agents in the treatment of multiple myeloma. IV. L-Phenylalanine mustard (NSC-8806). Cancer Chemother Rep 21(87):99

    Google Scholar 

  • Bergsagel DE, Bailey AJ, Langley GR, MacDonald RN, White DF, Miller AB (1979) The chemotherapy on plasma-cell myeloma and the incidence of acute leukemia. N Engl J Med 301(14):743–748

    PubMed  CAS  Article  Google Scholar 

  • Blade J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G et al (1998) Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematology 102(5):1115–1123

    Article  CAS  Google Scholar 

  • Blumenstengel K, Ruffert K, Frincke HJ, Kath R, Höffken K (1998) Bendamustine vs. Melphalan in the primary treatment of multiple myeloma (MM). A randomized prospective study. J Cancer Res Clin Oncol 124:68

    Google Scholar 

  • Bosanquet AG, Gilby ED (1982) Pharmacokinetics of oral and intravenous melphalan during routine treatment of multiple myeloma. Eur J Cancer Clin Oncol 18(4):355–362

    PubMed  Article  CAS  Google Scholar 

  • Durie BG, Salmon SE (1975) A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer 36(3):842–854

    PubMed  Article  CAS  Google Scholar 

  • Ehrsson H, Eksborg S, Osterborg A, Mellstedt H, Lindfors A (1989) Oral melphalan pharmacokinetics–relation to dose in patients with multiple myeloma. Med Oncol Tumor Pharmacother 6(2):151–154

    PubMed  CAS  Google Scholar 

  • Fernberg JO, Johansson B, Lewensohn R, Mellstedt H (1990) Oral dosage of melphalan and response to treatment in multiple myeloma. Eur J Cancer 26(3):393–396

    PubMed  CAS  Article  Google Scholar 

  • Gahrton G, Svensson H, Cavo M, Apperley J, Bacigalupo A, Bjorkstrand B et al (2001) Progress in allogenic bone marrow and peripheral blood stem cell transplantation for multiple myeloma: a comparison between transplants performed 1983–1993 and 1994–1998 at European Group for Blood and Marrow Transplantation centres. Br J Haematol 113(1):209–216

    PubMed  Article  CAS  Google Scholar 

  • Greenlee RT, Hill-Harmon MB, Murray T, Thun M (2001) Cancer statistics 2001. CA Cancer J Clin 51(1):15–36

    PubMed  CAS  Article  Google Scholar 

  • Gregory WM, Richards MA, Malpas JS (1992) Combination chemotherapy versus melphalan and prednisolone in the treatment of multiple myeloma: an overview of published trials. J Clin Oncol 10(2):334–342

    PubMed  CAS  Google Scholar 

  • Harousseau J-L, Attal M, Divine M, Marit G, Leblond V, Stoppa A-M et al (1995) Autologous stem cell transplantation after first remission induction treatment in multiple myeloma: a report of the French Registry on autologous transplantation in multiple myeloma. Blood 85(11):3077–3085

    PubMed  CAS  Google Scholar 

  • Hoeffken K, Merkle K, Schoenfelder M, Anger G, Brandtner M, Ridwelski K et al (1998) Bendamustine as salvage treatment in patients with advanced progressive breast cancer: a phase II study. J Cancer Res Clin Oncol 124(11):627–632

    Article  CAS  Google Scholar 

  • Kyle RA (1975) Multiple myeloma: review of 869 cases. Mayo Clin Proc 50:29–40

    PubMed  CAS  Google Scholar 

  • Leoni LM, Bailey B, Reifert J, Niemeyer C, Bendall H, Dauffenbach L et al (2003) SDX-105 (Bendamustine), a clinically active antineoplastic agent posesses a unique mechanism of action. Blood 102(11):640a

    Google Scholar 

  • Myeloma Trialists’ Collaborative Group (1998) Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. J Clin Oncol 16(12):3832–3842

    Google Scholar 

  • Oken MM (1994) Standard treatment of multiple myeloma. Mayo Clin Proc 69(8):781–786

    PubMed  CAS  Google Scholar 

  • Peest D, Coldewey R, Deicher H, Sailer M, Vykoupil C, Leo R et al (1993) Prognostic value of clinical, laboratory, and histological characteristics in multiple myeloma: improved definition of risk groups. Eur J Cancer 29A(7):978–983

    PubMed  Article  CAS  Google Scholar 

  • Peest D, Deicher H, Coldewey R, Leo R, Bartl R, Bartels H et al (1995) A comparison of polychemotherapy and melphalan/prednisone for primary remission induction, and interferon-alpha for maintenance treatment, in multiple myeloma. A prospective trial of the German Myeloma Treatment Group. Eur J Cancer 31A(2):146–151

    PubMed  Article  CAS  Google Scholar 

  • Raaijmakers HGP, Izquierdo MAI, Lokhorst HM, de Leeuw C, Belien JAM, Bloem AC et al (1998) Lung-resistance-related protein expression is a negative predictive factor for response to conventional low but not to intensified dose alkylating chemotherapy in multiple myeloma. Blood 91(3):1029–1036

    PubMed  CAS  Google Scholar 

  • Raje N, Anderson KC (2000) Multiple myeloma. Curr Treat Options Oncol 1(1):73–82

    PubMed  Article  CAS  Google Scholar 

  • Richardson PC, Barlogie B, Berenson J, Sighal S, Jagannath S, Irwin D et al (2003) A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 348(26):2609–2617

    PubMed  Article  CAS  Google Scholar 

  • Strumberg D, Harstrick A, Doll K, Hoffmann B, Seeber S (1996) Bendamustine hydrochloride activity against doxorubicin-resistant human breast carcinoma cell lines. Anticancer Drugs 7(4):415–421

    PubMed  Article  CAS  Google Scholar 

  • Vesole DH, Tricot G, Jagannath S, Desikan KR, Siegel D, Bracy D et al (1996) Autotransplants in multiple myeloma: what have we learned? Blood 88(3):838–847

    PubMed  CAS  Google Scholar 

  • Weber DM (2002) Newly diagnosed multiple myeloma. Curr Treat Options Oncol 3(3):235–245

    PubMed  Article  Google Scholar 

Download references

Acknowledgements

The authors wish to thank Barbara Hobbie for manuscript preparation, and all physicians, nurses, and support personnel for their care of patients on this study.

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Authors and Affiliations

  1. Department of Hematology and Oncology, University of Leipzig, Johannisallee 32A, 04103, Leipzig, Germany

    W. Pönisch, W. Helbig & D. Niederwieser

  2. Department of Hematology and Oncology, University of Frankfurt, Frankfurt, Germany

    P. S. Mitrou

  3. Ribosepharm GmbH, Munich, Germany

    K. Merkle

  4. Division of Hematology and Oncology, HELIOS Klinikum, Erfurt, Germany

    M. Herold & A. Schulze

  5. Hospital Riesa, Riesa, Germany

    M. Assmann

  6. Harz-Klinikum Wernigerode GmbH, Wernigerode, Germany

    G. Wilhelm

  7. Division of Hematology and Oncology, Südharz Hospital Nordhausen, Nordhausen, Germany

    K. Dachselt

  8. Community Hospital, Zella-Mehlis, Germany

    P. Richter

  9. Division of Hematology and Oncology, Vogtland-Klinikum Plauen, Plauen, Germany

    V. Schirmer

  10. Division of Hematology and Oncology, HELIOS Klinikum, Schwerin, Germany

    R. Šubert

  11. Division of Hematology and Oncology, Hospital Johann Kentmann, Torgau, Germany

    B. Harksel

  12. Division of Hematology and Oncology, Hospital Neu Brandenburg, Brandenburg, Germany

    N. Grobe

  13. Division of Hematology and Oncology, Waldklinikum Gera, Gera, Germany

    E. Stelzer

  14. Division of Hematology and Oncology, Hematology and Oncology Zittau, Zittau, Germany

    M. Schulze

  15. Hematology and Oncology, Erfurt, Germany

    A. Bittrich

  16. Division of Hematology and Oncology, University Rostock, Rostock, Germany

    M. Freund

  17. Division of Hematology and Oncology, Ernst von Bergmann Hospital Postdam, Postdam, Germany

    R. Pasold

  18. Institute of Patology, University Leipzig, Leipzig, Germany

    Th. Friedrich

Authors
  1. W. Pönisch
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  2. P. S. Mitrou
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  3. K. Merkle
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  4. M. Herold
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  5. M. Assmann
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  6. G. Wilhelm
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  7. K. Dachselt
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  8. P. Richter
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  9. V. Schirmer
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  10. A. Schulze
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  11. R. Šubert
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  12. B. Harksel
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  13. N. Grobe
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  14. E. Stelzer
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  15. M. Schulze
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  16. A. Bittrich
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  17. M. Freund
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  18. R. Pasold
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  19. Th. Friedrich
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  20. W. Helbig
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  21. D. Niederwieser
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Corresponding author

Correspondence to D. Niederwieser.

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Pönisch, W., Mitrou, P.S., Merkle, K. et al. Treatment of Bendamustine and Prednisone in patients with newly diagnosed multiple myeloma results in superior complete response rate, prolonged time to treatment failure and improved quality of life compared to treatment with Melphalan and Prednisone—a randomized phase III study of the East German Study Group of Hematology and Oncology (OSHO). J Cancer Res Clin Oncol 132, 205–212 (2006). https://doi.org/10.1007/s00432-005-0074-4

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  • DOI: https://doi.org/10.1007/s00432-005-0074-4

Keywords

  • Bendamustine
  • Prednisone
  • Multiple myeloma
  • Melphalan
  • Prednisone