Fermé, Christophe, Thomas, José, Brice, Pauline, Casasnovas, Olivier, Vranovsky, Andrej, Bologna, Serge, Lugtenburg, Pieternella J, Bouabdallah, Réda, Carde, Patrice, Sebban, Catherine, Eghbali, Houchingue, Salles, Gilles, Van Imhoff, Gustaaf W., Thyss, Antoine, Noordijk, Evert M., Reman, Oumédaly, Lybeert, Marnix L.M., Janvier, Maud, Spina, Michele, Audhuy, Bruno, Raemaekers, John M M, Delarue, Richard, Anglaret, Bruno, de Weerdt, Okke, Marjanovic, Zora, Tersteeg, Robbert J.H.A., de Jong, Daphne, Brière, Josette, Henry-Amar, Michel, for the European Organisation for Research and Treatment of Cancer Lymphoma Group, and, Hématologie, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Université Grenoble Alpes ( UGA ), Laboratoire de Psychologie et NeuroCognition ( LPNC ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Département d'Hematologie, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Gustave Roussy ( IGR ), Hematologie, Université Bordeaux Segalen - Bordeaux 2, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Haematology, University Medical Center Groningen, CHU Nice, Hôpital Georges Clémenceau, Department of Radiation Oncology, Catharina Hospital, Laboratory of Information, Network and Communication Sciences ( LINCS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut Mines-Télécom [Paris], Service d'Hématologie, Hospices civils Colmar, Department of Haematology, Radboud University Medical Center [Nijmegen], Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Laboratoire d'Hématologie et d'Immunologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Calvados Cancer Registry, Centre Régional de Lutte contre le Cancer François Baclesse ( CRLC François Baclesse ), CCA - Cancer Treatment and quality of life, AGEM - Re-generation and cancer of the digestive system, Pathology, Hematology, Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Stem Cell Aging Leukemia and Lymphoma (SALL)
Purpose: For early-stage Hodgkin lymphoma (HL), optimal chemotherapy regimen and the number of cycles to be delivered remain to settle down. The H9-U trial compared three modalities of chemotherapy followed by involved-field radiotherapy (IFRT) in patients with stage I-II HL and risk factors (NCT00005584).Patients and methods: Patients aged 15-70 years with untreated supradiaphragmatic HL with at least one risk factor (age >= 50, involvement of 4-5 nodal areas, mediastinum/thoracic ratio >= 0.35, erythrocyte sedimentation rate (ESR) >= 50 without B-symptoms or ESR >= 30 and B-symptoms) were eligible for the randomised, open label, multicentre, non-inferiority H9-U trial. The limit of non-inferiority was set at 10% for the difference between 5-year event-free survival (EFS) estimates. From October 1998 to September 2002, 808 patients were randomised to receive either the control arm 6-ABVD-IFRT (n = 276), or one of the two experimental arms: 4-ABVD-IFRT (n = 277) or 4-BEACOPP(baseline)-IFRT (n = 255).Results: Results in the 4-ABVD-IFRT (5-year EFS, 85.9%) and the 4-BEACOPP(baseline)-IFRT (5-year EFS, 88.8%) were not inferior to 6-ABVD-IFRT (5-year EFS, 89.9%): difference of 4.0% (90% CI, -0.7%-8.8%) and of 1.1% (90% CI,-3.5%-5.6%) respectively. The 5-year overall survival estimates were 94%, 93%, and 93%, respectively. Patients treated with combined modality treatment chemotherapeutic regimen comprising doxorubicin (Adriamycin), bleomycin, vincristine (Oncovin), cyclophosphamide, procarbazine, etoposide and prednisone (BEACOPP)(baseline) more often developed serious adverse events requiring supportive measures and hospitalisation compared with patients receiving the chemotherapeutic regimen comprising doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD).Conclusions: The trial demonstrates that 4-ABVD followed by IFRT yields high disease control in patients with early-stage HL and risk factors responding to chemotherapy. Although non-inferior in terms of efficacy, four cycles of BEACOPP(baseline) were more toxic than four or six cycles of ABVD.