Skip to main content

Advertisement

SpringerLink
Log in

Bendamustine, vincristine and prednisone (BOP) versus cyclophosphamide, vincristine and prednisone (COP) in advanced indolent non-Hodgkin’s lymphoma and mantle cell lymphoma: results of a randomised phase III trial (OSHO# 19)

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose: The purpose of this study was to compare the efficacy and toxicity of bendamustine, vincristine + prednisone (BOP) with a standard regimen of cyclophosphamide, vincristine + prednisone (COP) in patients with previously untreated advanced indolent non-Hodgkin’s lymphoma (NHL) and mantle cell lymphoma. Methods: A total of 164 patients with follicular lymphoma (grade 1/2), mantle cell lymphoma or lymphoplasmacytic lymphoma (immunocytoma) was randomised to treatment with vincristine 2 mg (day 1) and prednisone 100 mg/m2 (days 1–5) + bendamustine 60 mg/m2 (days 1–5) or + cyclophosphamide 400 mg/m2 (days 1–5) for a total of eight 21-day cycles. Results: The rate of complete remission was 22% with BOP and 20% with COP. The projected 5-year survival rate was 61% with BOP and 46% with COP. The BOP-associated 5-year survival advantage almost reached significance in the subgroup of patients who responded to therapy (74% vs. 56%; P=0.05), and did reach significance in responders who did not receive interferon maintenance therapy (70% vs. 47%; P=0.03). Toxicity was acceptable in both treatment groups, although alopecia and leucopenia were more severe with COP. Conclusions: Bendamustine can efficaciously and safely replace cyclophosphamide, as used in standard COP therapy, for the treatment of patients with indolent NHL and mantle cell lymphoma. Long-term survival data suggest a clinically significant benefit for patients treated with BOP

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Bagley CM, Devita VT, Berard CW, Canellos GP (1972) Advanced lymphosarcoma: intensive cyclical combination chemotherapy with cyclophosphamide, vincristine, and prednisone. Ann Intern Med 76(2):227–234

    PubMed  Google Scholar 

  • Blumenstengel K, Fricke H-J, Kath R, Höffken K (1999) Bendamustine(B), vincristine(O), prednisolone(P) in relapsed and refractory low-grade non-Hodgkin’s lymphomas (NHL). Ann Hematol 77(Suppl 2):149 (Abstr 591)

    Google Scholar 

  • Bremer K (2002) High rates of long-lasting remissions after 5-day bendamustine chemotherapy cycles in pre-treated low-grade non-Hodgkin’s lymphomas. J Cancer Res Clin Oncol 128(11):603–609

    Article  PubMed  CAS  Google Scholar 

  • Bremer K, Roth W (1996) Bendamustine, a low toxic nitrogen-mustard derivative with high efficacy in malignant lymphomas. Tumordiagn u Ther 17:1–6

    Google Scholar 

  • Chow KU, Nowak D, Boehrer S, Ruthardt M, Knau A, Hoelzer D, Mitrou PS, Weidmann E (2003) Synergistic effects of chemotherapeutic drugs in lymphoma cells are associated with down-regulation of inhibitor of apoptosis proteins (IAPs), prostate-apoptosis-response-gene 4 (Par-4), death-associated protein (Daxx) and with enforced caspase activation. Biochem Pharmacol 66(5):711–724

    Article  PubMed  CAS  Google Scholar 

  • Dixon DO, McLaughlin P, Hagemeister FB, Freireich EJ, Fuller LM, Cabanillas FF, Gehan EA (1987) Reporting outcomes in Hodgkin’s disease and lymphoma. J Clin Oncol 5(10):1670–1672

    PubMed  CAS  Google Scholar 

  • Harris NL, Jaffe ES, Stein H (1994) A revised European-American classification of lymphoid neoplasm: a proposal from the International Lymphoma Study Group. Blood 84(5):1361–1392

    PubMed  CAS  Google Scholar 

  • Heider A, Niederle N (2001) Efficacy and toxicity of bendamustine in patients with relapsed low-grade non-Hodgkin’s lymphomas. Anticancer Drugs 12(9):725–729

    Article  PubMed  CAS  Google Scholar 

  • Herold M, Pasold R, Srock S, Neser S, Niederwieser D, Neubauer A, Dölken G, Naumann R, Fietz T, Freund M, Rohrberg R, Hoeffken K, Franke A, Ittel TH, Kettner E, Haak U, Mey U, Klinkenstein U, Assmann M, von Gruenhagen U, Dachselt K, Schwenke H, Bleyl D, Wolf H, Hahnfeld S, Hoffmann F-A, Lakner V, Richter P, Hähling D, Wolf HH, Eschenburg H, Clemens M-R, Grobe N (2004) Results of a prospective randomised open label phase iii study comparing rituximab plus mitoxantrone, chlorambucile, prednisolone chemotherapy (R-MCP) versus MCP alone in untreated advanced indolent non-hodgkin’s lymphoma (NHL) and mantle-cell-lymphoma (MCL). Blood 104(11):169a (Abstr 584)

    Google Scholar 

  • Hiddemann W, Schmoll H-J, Theml H, Hoffmann W (1999) Follikuläres Keimzentrumslymphom (zentroblastisch-zentrozystisches Lymphom). In: Schmoll, Höffken, Possinger (eds) Kompendium Internistische Onkologie, 3rd edn. Springer, Berlin, Heidelberg, New York, pp 279–296

    Google Scholar 

  • Hiddemann W, Forstpointner R, Kneba M, Schmitz N, Schmits R, Metzner B, Reiser M, Lengfelder E, Woermann B, Harder H, Hegewisch-Becker S, Bredel W, Hess G, Eimermacher H, Aldaoud A, Planker M, Rarwaresch R, Dreyling M, Unterhalt M (2004) The addition of rituximab to combination chemotherapy with CHOP has a long lasting impact on subsequent treatment in remission in follicular lymphoma but not in mantle cell lymphoma: results of two prospective randomized studies of the German Low Grade Lymphoma Study Group (GLSG) 104(11):50a (Abstr 161)

  • Karnekal S, Crain B, Elliott G, Singh S (2004) SDX-105 (Bendamustine) Inhibits Growth of SU-DHL-1 and Daudi lymphoma xenografts in SCID Mice. PROC AACR 45 (Abstr 4575)

  • Lennert K, Feller AC (1990) In: Histopathologie der non-Hodgkin-lymphome (nach der aktualisierten Kiel-Klassifikation), 2nd edn. Springer, Berlin, Heidelberg, New York, p 15

  • Leoni LM, Bailey B, Reifert J (2003) SDX-105 (Bendamustine), a clinically active antineoplastic agent possesses a unique mechanism of action. Blood 102(11):640a (Abstr 2363)

    Google Scholar 

  • Leoni LM, Bailey B, Reifert J, Niemeyer C, Bendall H, Dauffenbach L, Kerfoot C (2004) In vitro and ex vivo activity of SDX-105 (Bendamustine) in drug-resistant lymphoma cells. PROC AACR 45 (Abstr 1215)

  • Niemeyer C, Bailey B, Reifert J, Bendall H, Corbeil J, Leoni LM (2004) SDX-105 (Bendamustine) is a clinically active chemotherapeutic agent with a distinct mechanism of action. PROC AACR 45 (Abstr 1129)

  • Pötscher C, Hiller E, Busch M, Unterhalt M, Hiddemann W (2000) Aktuelle Therapiekonzepte follikulärer Lymphome (zentroblastisch-zentrozytisch). Akt Onkol 109:3–20

    Google Scholar 

  • Ruffert K (1999) Therapy of low grade non-Hodgkin’s-lymphoma (NHL) with bendamustine and oral etoposide. Ann Oncol 10(Suppl 3):125 (Abstr 452)

    Article  PubMed  Google Scholar 

  • Ruffert K, Jahn H, Syrbe G, Stauch M, Jorke D, Kühn R (1989) Cytostasan (Bendamustin) in der Alternativtherapie maligner Non-Hodgkin-Lymphome. Z Klin Med 44(8):671–674

    Google Scholar 

  • Rummel M-J, Al-Bartran S, Welslau M, Kofahl-Krause D, Duerk H, Hoelzer D, Mitrou PS (2005) Bendamustine and rituximab act synergistically in vitro and are effective in the treatment of relapsed or refractory indolent and mantle cell lymphomas. J Clin Oncol 23(16S):576s (Abstr 6565)

    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

    Article  PubMed  CAS  Google Scholar 

  • Unterhalt M, Hermann R, Koch P, Trümper L, Bodenstein H, Dietzfelbinger H, Landys K, Reuß M, Vetter H, Maschmeyer G, Freund M, Neubauer A, Engert A, Stauder R, Herold M, Tiemann M, Parwaresch R, Stein H, Hiddemann W (1996) Long term interferon alpha maintenance prolongs remission duration in advanced low grade lymphomas and is related to the efficacy of initial cytoreductive chemotherapy. Blood 88(Suppl 1):453a (Abstr 1801)

    Google Scholar 

  • Vose JM (1998) Current approaches to the management of non Hodgkin’s lymphoma. Semin Oncol 25(4):483–491

    PubMed  CAS  Google Scholar 

  • Vose, JM (1999) Mantle cell lymphoma. In: Non-Hodgkin’s lymphoma: treatment for the millenium. Proceedings of a symposium at the 41st annual meeting of the American Society of Hematology, New Orleans

  • Weide R, Pandorf A, Heymanns J, Köppler H (2004) Bendamustine/Mitoxantrone/Rituximab (BMR): a very effective, well tolerated outpatient chemoimmunotherapy for relapsed and refractory CD20-positive indolent malignancies. Final results of a pilot study. Leuk Lymphoma 45(12):2445–2449

    Article  PubMed  CAS  Google Scholar 

  • Weissinger F, Kreipe HH, Wilhelm M (1997) Non hodgkin lymphome. Internist 38:1131–1142

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. HELIOS Klinikum Erfurt GmbH, 2. Medizinische Klinik, Bereich Hämatologie/Onkologie, Nordhäuserstr. 74, 99089, Erfurt, Germany

    M. Herold & A. Schulze

  2. Universitätsklinikum Leipzig,  , Germany

    D. Niederwieser

  3. Universitätsklinikum Magdeburg,  , Germany

    A. Franke

  4. Universitätsklinikum Jena,  , Germany

    H. J. Fricke

  5. Bezirkskrankenhaus Zella-Mehlis,  , Germany

    P. Richter

  6. Universitätsklinikum Rostock,  , Germany

    M. Freund

  7. Bezirkskrankenhaus Eisenach,  , Germany

    B. Ismer

  8. Südharz Krankenhaus Nordhausen,  , Germany

    K. Dachselt

  9. St. Hedwig Krankenhaus Berlin,  , Germany

    C. Boewer

  10. Vogtlandklinik Plauen,  , Germany

    V. Schirmer

  11. Gemeinschaftspraxis Hämatologie/Onkologie Erfurt,  , Germany

    J. Weniger

  12. Klinikum Ernst von Bergmann Potsdam,  , Germany

    R. Pasold

  13. Bezirkskrankenhaus Wittenberg,  , Germany

    C. Winkelmann

  14. Medizinisches Zentrum Frankfurt/Oder,  , Germany

    C. Klinkenstein

  15. Bezirkskrankenhaus Zittau,  , Germany

    M. Schulze

  16. Gemeinschaftspraxis Hämatologie/Onkologie Meißen,  , Germany

    H. Arzberger

  17. Augusta Krankenanstalt Bochum,  , Germany

    K. Bremer

  18. Gemeinschaftspraxis Hämatologie/Onkologie Jena,  , Germany

    S. Hahnfeld

  19. Gemeinschaftspraxis Hämatologie/Onkologie Leipzig,  , Germany

    A. Schwarzer

  20. Gemeinschaftspraxis Hämatologie/Onkologie Arnstadt,  , Germany

    C. Müller

  21. Katholisches Krankenhaus Erfurt,  , Germany

    Chr. Müller

Authors
  1. M. Herold
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Schulze
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Niederwieser
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Franke
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. J. Fricke
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P. Richter
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Freund
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. B. Ismer
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. K. Dachselt
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. C. Boewer
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. V. Schirmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. J. Weniger
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. R. Pasold
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. C. Winkelmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. C. Klinkenstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. M. Schulze
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. H. Arzberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. K. Bremer
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. S. Hahnfeld
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. A. Schwarzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. C. Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Chr. Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

for the East German Study Group Hematology and Oncology (OSHO)

Corresponding author

Correspondence to M. Herold.

Additional information

Funding support: Supported by a grant from ribosepharm GmbH, Clinical Research, Munich.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Herold, M., Schulze, A., Niederwieser, D. et al. Bendamustine, vincristine and prednisone (BOP) versus cyclophosphamide, vincristine and prednisone (COP) in advanced indolent non-Hodgkin’s lymphoma and mantle cell lymphoma: results of a randomised phase III trial (OSHO# 19). J Cancer Res Clin Oncol 132, 105–112 (2006). https://doi.org/10.1007/s00432-005-0023-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-005-0023-2

Keywords

Search

Navigation