Originally published as JCO Early Release 10.1200/JCO.2008.19.8820 on August 24 2009

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Escalated-Dose BEACOPP in the Treatment of Patients With Advanced-Stage Hodgkin's Lymphoma: 10 Years of Follow-Up of the GHSG HD9 Study

From the Klinik I für Innere Medizin, Universitätsklinik Köln; German Hodgkin Study Group, Klinik I für Innere Medizin, Universitätsklinik Köln; Institut für Medizinische Statistik, Informatik und Epidemiologie, Universität Köln, Köln; Charité, Universitätsmedizin, Innere Klinik, Schwerpunkt Onkologie/Hämatologie; HELIOS Klinikum Berlin-Buch, Robert-Rössle Klinik, Charité Campus Buch, Klinik für Hämatologie, Onkologie und Tumorimmunologie; Charité Campus Mitte, Medizinische Klinik und Poliklinik II, Berlin; Universitätsklinikum Münster, Medizinische Klinik und Poliklinik A, Münster; Klinikum Chemnitz GmbH, Klinik für Innere Medizin III, Chemnitz; Universitätsklinikum Magdeburg, Zentrum für Innere Medizin, Klinik für Hämatologie/Onkologie, Magdeburg; Universitätskliniken des Saarlandes, Medizinische Klinik und Poliklinik, Innere Medizin I, Homburg/Saar; Klinikum Nürnberg Nord, Medizinische Klinik 5, Schwerpunkt Hämatologie und Onkologie, Nürnberg; Universitätsklinikum Göttingen, Klinik für Hämatologie und Onkologie, Göttingen; Robert-Bosch Krankenhaus Stuttgart, Klinik für Hämatologie, Onkologie und Klinische Immunologie, Stuttgart; Städtisches Klinikum Karlsruhe, Medizinische Klinik II, Abteilung für Hämatologie und Onkologie, Karlsruhe; Universitätsklinikum Giessen und Marburg, Medizinische Klinik und Poliklinik IV, Giessen; Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Ludwig-Maximilians-Universität München, München; Institut für Pathologie, Universitätsklinikum Würzburg, Würzburg; Institut für Medizinische Informatik, Statistik u. Epidemiologie, Universität Leipzig, Leipzig, Germany; and the Swiss Group for Clinical Cancer Research, Bern, Switzerland.

Corresponding author: Andreas Engert, MD, Klinik I für Innere Medizin, Universitätsklinik Köln, Kerpener Straße 62, 50931 Köln, Germany; e-mail: a.engert{at}uni-koeln.de.

Purpose The HD9 trial of the German Hodgkin Study Group compared two different doses (baseline and escalated) of the bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) chemotherapy regimen in 1,196 patients with advanced-stage Hodgkin's lymphoma (HL). The previous analysis with 5 years median follow-up had indicated improved tumor control with BEACOPP escalated. Since the long-term safety and efficacy of this regimen has been debated, we report the 10-year follow-up.

Patients and Methods Patients received one of three chemotherapy regimens: eight cycles of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD); eight cycles of BEACOPP baseline; or eight cycles of BEACOPP escalated.

Results Median follow-up was 111 months. At 10 years, freedom from treatment failure (FFTF) was 64%, 70%, and 82% with OS rates of 75%, 80%, and 86% for patients treated with COPP/ABVD (arm A), BEACOPP baseline (arm B), and BEACOPP escalated (arm C), respectively (P < .001). BEACOPP escalated was significantly better than BEACOPP baseline in terms of FFTF (P < .0001) and OS (P = .0053). A total of 74 second malignancies (6.2%) were documented, including acute myeloid leukemia (0.4%, 1.5%, and 3.0%), non-Hodgkin's lymphoma (2.7%, 1.7%, and 1.0%), and solid tumors (2.7%, 3.4%, and 1.9%). The corresponding overall secondary malignancy rates were 5.7%, 6.6%, and 6.0%, respectively.

Conclusion The 10-year follow-up of the HD9 trial demonstrates a stabilized significant improvement in long-term FFTF and OS for BEACOPP escalated in advanced-stage HL. These results challenge ABVD as standard of care for this patient population.

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

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