Christophe Fermé1, José Thomas2, Pauline Brice3, Olivier Casasnovas4, Andrej Vranovsky5, Serge Bologna6, Pieternella J Lugtenburg7, Réda Bouabdallah8, Patrice Carde1, Catherine Sebban9, Houchingue Eghbali10, Gilles Salles11, Gustaaf W van Imhoff12, Antoine Thyss13, Evert M Noordijk14, Oumédaly Reman15, Marnix L M Lybeert16, Maud Janvier17, Michele Spina18, Bruno Audhuy19, John M M Raemaekers20, Richard Delarue21, Bruno Anglaret22, Okke de Weerdt23, Zora Marjanovic24, Robbert J H A Tersteeg25, Daphne de Jong26, Josette Brière3, Michel Henry-Amar27. 1. Gustave Roussy, 114 Rue Édouard Vaillant, 94805 Villejuif Cedex, France. 2. University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. 3. Centre Hospitalier Universitaire, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010 Paris, France. 4. Centre Hospitalier Universitaire, Hôpital du Bocage, 1 Boulevard Jeanne d'Arc, 21000 Dijon, France. 5. National Cancer Institute, Klenova 1, 83310 Bratislava, Slovakia. 6. Centre Hospitalier Universitaire de Nancy, Hôpital Brabois, Rue du Morvan, 54511 Vandœuvre-lès-Nancy, France. 7. Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. 8. Institut Paoli Calmettes, 232 Boulevard Sainte-Marguerite, BP156, 13273 Marseille Cedex 09, France. 9. Centre Léon Bérard, 28 Rue Laennec, 69373 Lyon Cedex 8, France. 10. Institut Bergonié, 229 Cours de l'Argonne, CS 61283, 33076 Bordeaux Cedex, France. 11. Centre Hospitalier Lyon Sud, Chemin du Grand Revoyet, 69310 Pierre-Bénite, France. 12. University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. 13. Centre Antoine Lacassagne, 33 Avenue de Valombrose, 06189 Nice Cedex 2, France. 14. Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. 15. Centre Hospitalier Universitaire, Avenue de la Côte de Nacre, 14033 Caen, France. 16. Catharina Ziekenhuis, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands. 17. Institut Curie-Hôpital René-Huguenin, 35 Rue Dailly, 92210 Saint-Cloud, France. 18. Centro di Riferimento Oncologico, Via Franco Gallini, 2, 33081 Aviano, PN, Italy. 19. Hôpitaux Civils de Colmar, Hôpital Pasteur, 39 Avenue de la Liberté, 68024 Colmar Cedex, France. 20. Radboud University Nijmegen Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands. 21. Centre Hospitalier Universitaire, Hôpital Necker, 149 Rue de Sèvres, 75015 Paris, France. 22. Centre Hospitalier de Valence, 179 Avenue du Maréchal Juin, 26953 Valence, France. 23. St. Antonius Ziekenhuis Nieuwegein, Koekoekslaan 1, 3435 CM Nieuwegein, The Netherlands. 24. Centre Hospitalier Universitaire, Hôpital Saint-Antoine, 184 Rue du faubourg Saint-Antoine, 75012 Paris, France. 25. University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. 26. VU University Medical Center, Department of Pathology, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands. 27. Centre de Traitement des Données du Cancéropôle Nord-Ouest, Centre François Baclesse, 3 Avenue Général Harris, 14076 Caen Cedex 05, France. Electronic address: m.henry.amar@baclesse.unicancer.fr.
Abstract
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-BEACOPPbaseline-IFRT (n = 255). RESULTS: Results in the 4-ABVD-IFRT (5-year EFS, 85.9%) and the 4-BEACOPPbaseline-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 BEACOPPbaseline were more toxic than four or six cycles of ABVD.
RCT Entities:
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-BEACOPPbaseline-IFRT (n = 255). RESULTS: Results in the 4-ABVD-IFRT (5-year EFS, 85.9%) and the 4-BEACOPPbaseline-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 BEACOPPbaseline were more toxic than four or six cycles of ABVD.