Journal of Cancer Research and Clinical Oncology

, Volume 132, Issue 2, pp 105–112

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)

  • M. Herold
  • A. Schulze
  • D. Niederwieser
  • A. Franke
  • H. J. Fricke
  • P. Richter
  • M. Freund
  • B. Ismer
  • K. Dachselt
  • C. Boewer
  • V. Schirmer
  • J. Weniger
  • R. Pasold
  • C. Winkelmann
  • C. Klinkenstein
  • M. Schulze
  • H. Arzberger
  • K. Bremer
  • S. Hahnfeld
  • A. Schwarzer
  • C. Müller
  • Chr. Müller
  • for the East German Study Group Hematology and Oncology (OSHO)
Original Paper

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

Keywords

Bendamustine Cyclophosphamide Indolent non-Hodgkin’s lymphoma Prednisone Vincristine Mantle cell lymphoma 

References

  1. 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):227–234PubMedGoogle Scholar
  2. 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
  3. 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):603–609CrossRefPubMedGoogle Scholar
  4. Bremer K, Roth W (1996) Bendamustine, a low toxic nitrogen-mustard derivative with high efficacy in malignant lymphomas. Tumordiagn u Ther 17:1–6Google Scholar
  5. 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):711–724CrossRefPubMedGoogle Scholar
  6. 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):1670–1672PubMedGoogle Scholar
  7. 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):1361–1392PubMedGoogle Scholar
  8. Heider A, Niederle N (2001) Efficacy and toxicity of bendamustine in patients with relapsed low-grade non-Hodgkin’s lymphomas. Anticancer Drugs 12(9):725–729CrossRefPubMedGoogle Scholar
  9. 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
  10. 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 279–296Google Scholar
  11. 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)Google Scholar
  12. 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)Google Scholar
  13. Lennert K, Feller AC (1990) In: Histopathologie der non-Hodgkin-lymphome (nach der aktualisierten Kiel-Klassifikation), 2nd edn. Springer, Berlin, Heidelberg, New York, p 15Google Scholar
  14. 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
  15. 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)Google Scholar
  16. 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)Google Scholar
  17. Pötscher C, Hiller E, Busch M, Unterhalt M, Hiddemann W (2000) Aktuelle Therapiekonzepte follikulärer Lymphome (zentroblastisch-zentrozytisch). Akt Onkol 109:3–20Google Scholar
  18. 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)CrossRefPubMedGoogle Scholar
  19. 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):671–674Google Scholar
  20. 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)CrossRefGoogle Scholar
  21. 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):415–421PubMedCrossRefGoogle Scholar
  22. 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
  23. Vose JM (1998) Current approaches to the management of non Hodgkin’s lymphoma. Semin Oncol 25(4):483–491PubMedGoogle Scholar
  24. 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 OrleansGoogle Scholar
  25. 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):2445–2449CrossRefPubMedGoogle Scholar
  26. Weissinger F, Kreipe HH, Wilhelm M (1997) Non hodgkin lymphome. Internist 38:1131–1142CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • M. Herold
    • 1
  • A. Schulze
    • 1
  • D. Niederwieser
    • 2
  • A. Franke
    • 3
  • H. J. Fricke
    • 4
  • P. Richter
    • 5
  • M. Freund
    • 6
  • B. Ismer
    • 7
  • K. Dachselt
    • 8
  • C. Boewer
    • 9
  • V. Schirmer
    • 10
  • J. Weniger
    • 11
  • R. Pasold
    • 12
  • C. Winkelmann
    • 13
  • C. Klinkenstein
    • 14
  • M. Schulze
    • 15
  • H. Arzberger
    • 16
  • K. Bremer
    • 17
  • S. Hahnfeld
    • 18
  • A. Schwarzer
    • 19
  • C. Müller
    • 20
  • Chr. Müller
    • 21
  • for the East German Study Group Hematology and Oncology (OSHO)
    • 21
  1. 1.HELIOS Klinikum Erfurt GmbH, 2. Medizinische KlinikBereich Hämatologie/OnkologieErfurtGermany
  2. 2.Universitätsklinikum Leipzig Germany
  3. 3.Universitätsklinikum Magdeburg Germany
  4. 4.Universitätsklinikum Jena Germany
  5. 5.Bezirkskrankenhaus Zella-Mehlis Germany
  6. 6.Universitätsklinikum Rostock Germany
  7. 7.Bezirkskrankenhaus Eisenach Germany
  8. 8.Südharz Krankenhaus Nordhausen Germany
  9. 9.St. Hedwig Krankenhaus Berlin Germany
  10. 10.Vogtlandklinik Plauen Germany
  11. 11.Gemeinschaftspraxis Hämatologie/Onkologie Erfurt Germany
  12. 12.Klinikum Ernst von Bergmann Potsdam Germany
  13. 13.Bezirkskrankenhaus Wittenberg Germany
  14. 14.Medizinisches Zentrum Frankfurt/Oder Germany
  15. 15.Bezirkskrankenhaus Zittau Germany
  16. 16.Gemeinschaftspraxis Hämatologie/Onkologie Meißen Germany
  17. 17.Augusta Krankenanstalt Bochum Germany
  18. 18.Gemeinschaftspraxis Hämatologie/Onkologie Jena Germany
  19. 19.Gemeinschaftspraxis Hämatologie/Onkologie Leipzig Germany
  20. 20.Gemeinschaftspraxis Hämatologie/Onkologie Arnstadt Germany
  21. 21.Katholisches Krankenhaus Erfurt Germany

Personalised recommendations