Originally published as JCO Early Release 10.1200/JCO.2005.05.2746 on June 5 2006

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Combined-Modality Therapy for Clinical Stage I or II Hodgkin's Lymphoma: Long-Term Results of the European Organisation for Research and Treatment of Cancer H7 Randomized Controlled Trials

Evert M. Noordijk, Patrice Carde, Noëlle Dupouy, Anton Hagenbeek, Augustinus D.G. Krol, Johanna C. Kluin-Nelemans, Umberto Tirelli, Mathieu Monconduit, José Thomas, Houchingue Eghbali, Berthe M.P. Aleman, Jacques Bosq, Marjeta Vovk, Tom A.M. Verschueren, Anne-Marie Pény, Théodore Girinsky, John M.M. Raemaekers, Michel Henry-Amar

From the Departments of Radiotherapy and Hematology, Leiden University Medical Center, Leiden; Departments of Hematology and Radiotherapy, Daniël den Hoed Cancer Center, Rotterdam; Department of Radiotherapy, Netherlands Cancer Institute, Amsterdam; Department of Radiotherapy, Radiotherapeutisch Instituut Limburg, Heerlen; Department of Hematology, University Medical Center Nijmegen, Nijmegen, the Netherlands; Departments of Medical Oncology, Radiotherapy, Pathology, and Biostatistics and Epidemiology, Institut Gustave Roussy, Villejuif; Department of Medical Oncology, Centre Henri Becquerel, Rouen; Department of Hematology, Institut Bergonié, Bordeaux; Department of Hematology and the Clinical Research Unit, Centre François Baclesse, Caen, France; Department of Medical Oncology, Centro di Riferimento Oncologico, Aviano, Italy; Department of Oncology, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium; and Department of Medical Oncology, Institute of Oncology, Ljubljana, Slovenija

Address reprint requests to Evert M. Noordijk, MD, Department of Radiotherapy, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands; e-mail: e.m.noordijk{at}lumc.nl

PURPOSE: In early-stage Hodgkin's lymphoma (HL), subtotal nodal irradiation (STNI) and combined chemotherapy/radiotherapy produce high disease control rates but also considerable late toxicity. The aim of this study was to reduce this toxicity using a combination of low-intensity chemotherapy and involved-field radiotherapy (IF-RT) without jeopardizing disease control.

PATIENTS AND METHODS: Patients with stage I or II HL were stratified into two groups, favorable and unfavorable, based on the following four prognostic factors: age, symptoms, number of involved areas, and mediastinal-thoracic ratio. The experimental therapy consisted of six cycles of epirubicin, bleomycin, vinblastine, and prednisone (EBVP) followed by IF-RT. It was randomly compared, in favorable patients, to STNI and, in unfavorable patients, to six cycles of mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP/ABV hybrid) and IF-RT.

RESULTS: Median follow-up time of the 722 patients included was 9 years. In 333 favorable patients, the 10-year event-free survival rates (EFS) were 88% in the EBVP arm and 78% in the STNI arm (P = .0113), with similar 10-year overall survival (OS) rates (92% v 92%, respectively; P = .79). In 389 unfavorable patients, the 10-year EFS rate was 88% in the MOPP/ABV arm compared with 68% in the EBVP arm (P < .001), leading to 10-year OS rates of 87% and 79%, respectively (P = .0175).

CONCLUSION: A treatment strategy for early-stage HL based on prognostic factors leads to high OS rates in both favorable and unfavorable patients. In favorable patients, the combination of EBVP and IF-RT can replace STNI as standard treatment. In unfavorable patients, EBVP is significantly less efficient than MOPP/ABV.

Preliminary results were presented in Noordijk EM, Carde P, Mandard AM, et al: Preliminary results of the EORTC-GPMC controlled clinical trial H7 in early-stage Hodgkin's disease. Ann Oncol 5:107-112, 1994.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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