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Equitoxicity of bolus and infusional etoposide: results of a multicenter randomised trial of the German High-Grade Non-Hodgkins Lymphoma Study Group (DSHNHL) in elderly patients with refractory or relapsing aggressive non-Hodgkin lymphoma using the CEMP regimen (cisplatinum, etoposide, mitoxantrone and prednisone)

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Abstract

To compare toxicity of etoposide bolus with continuous infusion and to assess the efficacy of the CEMP (cisplatinum, etoposide, mitoxantrone, prednisone) regimen, 47 patients with refractory or relapsed aggressive non-Hodgkin’s lymphoma older than 60 years (n = 43) or not qualifying for high-dose chemotherapy (n = 4) received five four-weekly CEMP cycles. Patients were randomised to start with bolus or continuous-infusion etoposide and then received bolus and infusional etoposide in an alternating fashion. The primary objective was the comparison of differences in the course of leukocytopenia and thrombocytopenia between the two application schedules. CEMP was well tolerated with little organ and moderate haematotoxicity. There was no difference in toxicity between bolus and continuous-infusion etoposide. Complete remission rate was 44% in patients relapsing ≥1 year, 27% in patients relapsing within the first year after achieving complete remission and 5% in primary refractory patients. Median event-free and overall survivals for all patients were 3 and 10 months, respectively. The observed equitoxicity and the more challenging logistics of a 60-h infusion make bolus injection the preferred application of etoposide. As the CEMP regimen is well tolerated and efficacious in elderly patients with relapsed or refractory aggressive non-Hodgkin’s lymphoma for whom more aggressive therapies are not feasible, a three-weekly modification of CEMP should be tested in combination with rituximab.

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Acknowledgements

This study was supported by Deutsche Krebshilfe. Data management: B. Mann, A. Schöler, U. Schönwiese, L. Martin Montanez, and W. Beck, M. Kunert, B. Wicklein. Statistical analysis: M. Löffler, M. Klöss, S. Zeynalova, D. Hasenclever. The following investigators and institutions recruited patients for this study: Hans-Jürgen Bias (Kreiskrankenhaus Waldbröl), Josef Birkmann (Klinikum Nürnberg), Heinrich Bodenstein (Klinikum Minden), Hermann Einsele (Universitätsklinik Würzburg), Ludwig Fischer von Weikersthal (Klinikum St. Marien Amberg), Roland Fuchs (St.-Antonius-Hospital Eschweiler), Johannes Grossmann (Evangelisches Krankenhaus Bethesda Mönchengladbach), Mathias Hänel (Klinikum Chemnitz), Martin Hoffmann (Klinikum der Stadt Ludwigshafen), Christian Kölbel (Krankenhaus der Barmherzigen Brüder Trier), Wilhelm Koch (Leopoldina-Krankenhaus Schweinfurt), Beate Krammer-Steiner (Klinikum Rostock Südstadt), Christiane Lange (Kliniken Maria Hilf, Krankenhaus St. Franziskus Mönchengladbach), Werner Langer (Kreiskrankenhaus Aurich), Walter Lindemann (Katholisches Krankenhaus Hagen), Peter Norbert Meier (Henriettenstift Hannover), Hans-Günther Mergenthaler (Katharinenhospital Stuttgart), Frank Odemar (Klinikum Bernburg), Roland Paliege (Klinikum Bad Hersfeld), Norma Peter (Carl-Thiem-Klinikum Cottbus), Michael Pfreundschuh (Universitätsklinikum des Saarlandes Homburg), Wolff Schmiegel (Universitätsklinik Bochum), Michael Schöttler (Martin-Luther-Krankenhaus Schleswig), Theo Scholten (Allgemeines Krankenhaus Hagen), Ulrich Stark (St.-Agnes-Hospital Bocholt), Frank Tympner (Kreiskrankenhaus Neumarkt).

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Authors and Affiliations

  1. Innere Medizin I, Universitätskliniken des Saarlandes, Homburg, Germany

    Carsten Zwick & Michael Pfreundschuh

  2. Medizinische Klinik V, Klinikum Nürnberg, Nürnberg, Germany

    Josef Birkmann

  3. Carl-Thiem-Klinikum Cottbus, Cottbus, Germany

    Norma Peter

  4. Abteilung Hämatologie, Klinikum Minden, Minden, Germany

    Heinrich Bodenstein

  5. St. Antonius-Hospital Eschweiler, Eschweiler, Germany

    Roland Fuchs

  6. Klinikum Chemnitz, Chemnitz, Germany

    Mathias Hänel

  7. Klinik für Innere Medizin, Universitätsklinikum Köln, Köln, Germany

    Marcel Reiser

  8. Innere Medizin IV, Universitätsklinikum Heidelberg, Heidelberg, Germany

    Manfred Hensel

  9. Onkologie, Mütterhaus, Trier, Germany

    Michael Clemens

  10. IMISE, Leipzig University, Leipzig, Germany

    Samira Zeynalova & Marita Ziepert

  11. DSHNHL Secretariat, 66421, Homburg, Germany

    Michael Pfreundschuh

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Zwick, C., Birkmann, J., Peter, N. et al. Equitoxicity of bolus and infusional etoposide: results of a multicenter randomised trial of the German High-Grade Non-Hodgkins Lymphoma Study Group (DSHNHL) in elderly patients with refractory or relapsing aggressive non-Hodgkin lymphoma using the CEMP regimen (cisplatinum, etoposide, mitoxantrone and prednisone). Ann Hematol 87, 717–726 (2008). https://doi.org/10.1007/s00277-008-0500-1

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