Originally published as JCO Early Release 10.1200/JCO.2008.17.0910 on January 5 2009

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ABVD Compared With BEACOPP Compared With CEC for the Initial Treatment of Patients With Advanced Hodgkin's Lymphoma: Results From the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial

From the Dipartimento di Oncologia ed Ematologia, Università di Modena e Reggio Emilia; Divisione di Ematologia e Trapianto di Midollo Osseo, Policlinico di Palermo; Unita Operativa (UO) Semplice di Oncoematologia, Divisione di Medicina, Ospedale "F. Miulli", Acquaviva delle Fonti; Divisione di Ematologia, Centro trapianti di Midollo Osseo, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza, S.G. Rotondo; UO di Ematologia, Azienda Ospedaliera Arcispedale S. Maria Nuova, Reggio Emilia; Divisione di Ematologia, Azienda Ospedaliera "Bianchi-Melacrino-Morelli", Reggio Calabria; Divisione di Ematologia, Casa di Cura La Maddalena, Palermo; UO Complessa di Ematologia, Presidio Ospedaliero V. Fazzi, Lecce; Ematologia e Trapianto di Cellule Staminali, IRCCS, Centro di Referimento Oncologico Della Basilicata, Rionero in Vulture; UO Ematologia 1/CMTO, Fondazione Ospedale Maggiore Policlinico Mare, IRCCS, Universita "Degli Studi, Milano"; UO Ematologia, Azienda Ospedaliera Universitaria Pisana, Pisa; Dipartimento di Ematologia, USL di Pescara, Ospedale S. Spirito, Pescara; Struttura Complessa di Ematologia, Azienda Ospedaliera "SS. Annunziata", Presidio Ospedaliero S.G. Moscati, Taranto; Divisione di Ematologia, Azienda Ospedaliera Papardo, Messina; and the Medicina Interna e Oncologia Medica, Università di Pavia, IRCCS Policlinico San Matteo, Pavia, Italy.

Corresponding author: Massimo Federico, MD, Dipartimento di Oncologia ed Ematologia, Centro Oncologico Modenese, Università di Modena e Reggio Emilia, Policlinico - Via del Pozzo 71, 41100 Modena, Italy; e-mail: federico{at}unimore.it.

Purpose To compare doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) versus bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) versus cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxirubicin, vincristine, procarbazine, vinblastine, and bleomycin (COPPEBVCAD; CEC) for advanced Hodgkin's lymphoma (HL).

Patients and Methods Three hundred seven patients with advanced HL (stage IIB, III, and IV) were randomly assigned to receive six courses of ABVD, four escalated plus two standard courses of BEACOPP, or six courses of CEC, plus a limited radiation therapy program.

Results After a median follow-up of 41 months, BEACOPP resulted in a superior progression-free survival (PFS), with a significant reduction in risk of progression (hazard ratio [HR] = 0.50) compared with ABVD. No differences between BEACOPP and CEC, or CEC and ABVD were observed. The 5-year PFS was 68% (95% CI, 56% to 78%), 81% (95% CI, 70% to 89%), and 78% (95% CI, 68% to 86%), for ABVD, BEACOPP, and CEC, respectively (BEACOPP v ABVD, P = .038; CEC v ABVD and BEACOPP v CEC, P = not significant [NS]). The 5-year overall survival was 84% (95% CI, 69% to 92%), 92% (95% CI, 84% to 96%), and 91% (95% CI, 81% to 96%) for ABVD, BEACOPP, and CEC, respectively (P = NS). BEACOPP and CEC resulted in higher rates of grade 3-4 neutropenia than ABVD (P = .016); BEACOPP was associated with higher rates of severe infections than ABVD and CEC (P = .003).

Conclusion As adopted in this study BEACOPP is associated with a significantly improved PFS compared with ABVD, with a predictable higher acute toxicity.

Supported in part by grants from the Associazione Angela Serra per la Ricerca sul Cancro, Modena, and the Gruppo Amici Dell'Ematologia, Reggio Emilia, Italy.

Presented in part at the 7th International Symposium on Hodgkin's Lymphoma, November 3-7, 2007, Cologne, Germany.

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

Clinical Trials repository link available on JCO.org.

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