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.

3rd Medical Department Paracelcus Medical University Salzburg Austria

Berlin Reference Center for Lymphoma and Haematopathology Berlin Germany

Cantonal Hospital of St Gallen St Gallen Switzerland and SAKK Swiss Group for Clinical Cancer Research Bern Switzerland

Charité Universitätsmedizin Berlin Campus Virchow Klinikum Berlin Germany

Cochrane Haematological Malignancies Group Department of Internal Medicine 1 University Hospital of Cologne Cologne Germany

Department of Haematology and Oncology Medical Centre Otto von Guericke University Magdeburg Magdeburg Germany

Department of Internal Medicine 1 University Hospital of Cologne Cologne Germany

Department of Internal Medicine 5 Haematology Oncology University of Erlangen Germany

Department of Radiation Oncology University Hospital of Cologne Cologne Germany

German Hodgkin Study Group Department of Internal Medicine 1 University Hospital of Cologne Cologne Germany

Katholisches Krankenhaus Hagen Germany

Klinik für Onkologie Katharinenhospital Stuttgart Germany

Klinikum Nürnberg Nürnberg Germany

Medizinische Klinik Hämatologie Onkologie Evangelisches Krankenhaus Hamm Germany

Medizinische Klinik Hämatologie Onkologie Immunologie Palliativmedizin St Vincentius Kliniken gAG Karlsruhe Germany

Medizinische Klinik Krankenanstalt Mutterhaus d Borromäerinnen Trier Germany

Medizinische Klinik Städtisches Klinikum Karlsruhe Germany

Medizinische Klinik Universitätsklinik Regensburg Regensburg Germany

Medizinische Klinik Universitätsklinik Schleswig Holstein Kiel Germany

University Hospital Kralovske Vinohrady 3rd Faculty of Medicine Charles University Prague Czech Republic

University Hospital Münster Münster Germany

University Hospital Würzburg Würzburg Germany

University of Heidelberg Heidelberg Germany

University of Tübingen Tübingen Germany

VU University Medical Center Amsterdam Netherlands

Zentrum für Innere Medizin Hämatologie Onkologie Charité Campus Mitte Berlin Germany

Lancet. 2015 Apr 11;385(9976):1371-3. doi: 10.1016/S0140-6736(14)61701-3. PubMed

Lancet. 2015 Apr 11;385(9976):1396. doi: 10.1016/S0140-6736(15)60720-6. PubMed

References provided by Crossref.org

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ISRCTN
ISRCTN63474366