Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin's lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial.

Autor:	Behringer K; German Hodgkin Study Group (GHSG), Department of Internal Medicine 1, University Hospital of Cologne, Cologne, Germany., Goergen H; German Hodgkin Study Group (GHSG), Department of Internal Medicine 1, University Hospital of Cologne, Cologne, Germany., Hitz F; Cantonal Hospital of St Gallen, St Gallen, Switzerland and SAKK Swiss Group for Clinical Cancer Research, Bern, Switzerland., Zijlstra JM; VU University Medical Center, Amsterdam, Netherlands., Greil R; Third Medical Department, Paracelcus Medical University, Salzburg, Austria., Markova J; University Hospital Kralovske Vinohrady, Third Faculty of Medicine, Charles University, Prague, Czech Republic., Sasse S; German Hodgkin Study Group (GHSG), Department of Internal Medicine 1, University Hospital of Cologne, Cologne, Germany., Fuchs M; German Hodgkin Study Group (GHSG), Department of Internal Medicine 1, University Hospital of Cologne, Cologne, Germany., Topp MS; University Hospital Würzburg, Würzburg, Germany., Soekler M; University of Tübingen, Tübingen, Germany., Mathas S; Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany., Meissner J; University of Heidelberg, Heidelberg, Germany., Wilhelm M; Klinikum Nürnberg, Nürnberg, Germany., Koch P; University Hospital Münster, Münster, Germany., Lindemann HW; Katholisches Krankenhaus, Hagen, Germany., Schalk E; Department of Haematology and Oncology, Medical Centre, Otto-von-Guericke University Magdeburg, Magdeburg, Germany., Semrau R; Department of Radiation Oncology, University Hospital of Cologne, Cologne, Germany., Kriz J; University Hospital Münster, Münster, Germany., Vieler T; Medizinische Klinik, Universitätsklinik Schleswig-Holstein, Kiel, Germany., Bentz M; Medizinische Klinik, Städtisches Klinikum Karlsruhe, Germany., Lange E; Medizinische Klinik, Hämatologie/Onkologie, Evangelisches Krankenhaus, Hamm, Germany., Mahlberg R; Medizinische Klinik, Krankenanstalt Mutterhaus d. Borromäerinnen, Trier, Germany., Hassler A; Zentrum für Innere Medizin, Hämatologie/Onkologie, Charité Campus Mitte, Berlin, Germany., Vogelhuber M; Medizinische Klinik, Universitätsklinik Regensburg, Regensburg, Germany., Hahn D; Klinik für Onkologie, Katharinenhospital, Stuttgart, Germany., Mezger J; Medizinische Klinik-Hämatologie, Onkologie, Immunologie, Palliativmedizin, St. Vincentius-Kliniken gAG, Karlsruhe, Germany., Krause SW; Department of Internal Medicine 5, Haematology/Oncology, University of Erlangen, Germany., Skoetz N; Cochrane Haematological Malignancies Group, Department of Internal Medicine 1, University Hospital of Cologne, Cologne, Germany., Böll B; German Hodgkin Study Group (GHSG), Department of Internal Medicine 1, University Hospital of Cologne, Cologne, Germany., von Tresckow B; German Hodgkin Study Group (GHSG), Department of Internal Medicine 1, University Hospital of Cologne, Cologne, Germany., Diehl V; German Hodgkin Study Group (GHSG), Department of Internal Medicine 1, University Hospital of Cologne, Cologne, Germany., Hallek M; Department of Internal Medicine 1, University Hospital of Cologne, Cologne, Germany., Borchmann P; German Hodgkin Study Group (GHSG), Department of Internal Medicine 1, University Hospital of Cologne, Cologne, Germany., Stein H; Berlin Reference Center for Lymphoma and Haematopathology, Berlin, Germany., Eich H; University Hospital Münster, Münster, Germany., Engert A; German Hodgkin Study Group (GHSG), Department of Internal Medicine 1, University Hospital of Cologne, Cologne, Germany. Electronic address: a.engert@uni-koeln.de.
Jazyk:	angličtina
Zdroj:	Lancet (London, England) [Lancet] 2015 Apr 11; Vol. 385 (9976), pp. 1418-27. Date of Electronic Publication: 2014 Dec 22.
DOI:	10.1016/S0140-6736(14)61469-0
Abstrakt:	Background: The role of bleomycin and dacarbazine in the ABVD regimen (ie, doxorubicin, bleomycin, vinblastine, and dacarbazine) has been questioned, especially for treatment of early-stage favourable Hodgkin's lymphoma, because of the drugs' toxicity. We aimed to investigate whether omission of either bleomycin or dacarbazine, or both, from ABVD reduced the efficacy of this regimen in treatment of Hodgkin's lymphoma. Methods: In this open-label, randomised, multicentre trial (HD13) we compared two cycles of ABVD with two cycles of the reduced-intensity regimen variants ABV (doxorubicin, bleomycin, and vinblastine), AVD (doxorubicin, vinblastine, and dacarbazine), and AV (doxorubicin and vinblastine), in patients with newly diagnosed, histologically proven, classic or nodular, lymphocyte predominant Hodgkin's lymphoma. In each treatment group, 30 Gy involved-field radiotherapy (IFRT) was given after both cycles of chemotherapy were completed. From Jan 28, 2003, patients were centrally randomly assigned (1:1:1:1) with a minimisation method to the four groups. Because of high event rates, assignment to the AV and ABV groups stopped early, on Sept 30, 2005, and Feb 10, 2006; assignment to ABVD and AVD continued (1:1) until Sept 30, 2009. Our primary objective was to show non-inferiority of the experimental variants compared with ABVD in terms of freedom from treatment failure (FFTF), by excluding a difference of 6% after 5 years corresponding to a hazard ratio (HR) of 1.72, via a 95% CI. Analyses reported here include qualified patients only, and between-group comparisons include only patients recruited during the same period. The trial was registered, number ISRCTN63474366. Findings: Of 1502 qualified patients, 566, 198, 571, and 167 were randomly assigned to receive ABVD, ABV, AVD, or AV, respectively. 5 year FFTF was 93.1%, 81.4%, 89.2%, and 77.1% with ABVD, ABV, AVD, and AV, respectively. Compared with ABVD, inferiority of the dacarbazine-deleted variants was detected with 5 year differences of -11.5% (95% CI -18.3 to -4.7; HR 2.06 [1.21 to 3.52]) for ABV and -15.2% (-23.0 to -7.4; HR 2.57 [1.51 to 4.40]) for AV. Non-inferiority of AVD compared with ABVD could also not be detected (5 year difference -3.9%, -7.7 to -0·1; HR 1.50, 1.00 to 2.26). 178 (33%) of 544 patients given ABVD had WHO grade III or IV toxicity, compared with 53 (28%) of 187 given ABV, 142 (26%) of 539 given AVD, and 40 (26%) of 151 given AV. Leucopenia was the most common event, and highest in the groups given bleomycin. Interpretation: Dacarbazine cannot be omitted from ABVD without a substantial loss of efficacy. With respect to our predefined non-inferiority margin, bleomycin cannot be safely omitted either, and the standard of care for patients with early-stage favourable Hodgkin's lymphoma should remain ABVD followed by IFRT. Funding: Deutsche Krebshilfe and Swiss State Secretariat for Education and Research. (Copyright © 2015 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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