Journal of Clinical Oncology, Vol 16, 3810-3821, Copyright © 1998 by American Society of Clinical Oncology

ARTICLES

BEACOPP, a new dose-escalated and accelerated regimen, is at least as effective as COPP/ABVD in patients with advanced-stage Hodgkin's lymphoma: interim report from a trial of the German Hodgkin's Lymphoma Study Group

V Diehl, J Franklin, D Hasenclever, H Tesch, M Pfreundschuh, B Lathan, U Paulus, M Sieber, JU Rueffer, M Sextro, A Engert, J Wolf, R Hermann, L Holmer, U Stappert-Jahn, E Winnerlein-Trump, G Wulf, S Krause, A Glunz, K von Kalle, H Bischoff, C Haedicke, E Duehmke, A Georgii and M Loeffler
Department of Internal Medicine, University of Cologne, Germany. v.diehl@uni-koeln.de

PURPOSE: The HD9 trial aims to evaluate whether moderate dose escalation and/or acceleration of standard polychemotherapy is beneficial for advanced-stage Hodgkin's disease (HD). Two variants of a novel bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) scheme (standard and escalated dose) are compared with cyclophosphamide, vincristine, procarbazine, and prednisone (COPP)/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). PATIENTS AND METHODS: The randomized, three-arm trial recruited patients in stages IIB and IIIA with risk factors and stages IIIB and IV. BEACOPP in baseline dose contains all drug dosages of COPP/ABVD (except vincristine and procarbazine) rearranged in a shorter, 3-week cycle. Escalated BEACOPP uses higher doses of cyclophosphamide, doxorubicin, and etoposide with granulocyte colony- stimulating factor (G-CSF) support. After eight chemotherapy cycles, initial bulky and residual disease is irradiated. The trial is monitored and analyzed by means of a sequential strategy. RESULTS: An interim analysis with 505 assessable patients and a median follow-up of 23 months showed a significant inferiority (according to sequential monitoring strategy) of the COPP/ABVD regimen in progression rate and freedom from treatment failure (FFTF) compared with the pooled results of both BEACOPP variants. The 24-month FFTF rate was 75% for COPP/ABVD and 84% for BEACOPP pooled (P = .034). There was 12% progressive disease with COPP/ABVD and 6% with BEACOPP pooled. Differences in survival were not significant in sequential analysis. The acute toxicity of baseline BEACOPP resembled that of COPP/ABVD; escalated BEACOPP showed increased but manageable hematologic toxicity. CONCLUSION: Combined with local irradiation, BEACOPP in one or both variants shows superior disease control compared with COPP/ABVD, with acceptable acute toxicity. Further follow-up is required to assess the effect of dosage and the effect on survival and late toxicities.

This article has been cited by other articles:

				A. Shimabukuro-Vornhagen, H. Haverkamp, A. Engert, L. Balleisen, P. Majunke, G. Heil, H. T. Eich, H. Stein, V. Diehl, and A. Josting Lymphocyte-Rich Classical Hodgkin's Lymphoma: Clinical Presentation and Treatment Outcome in 100 Patients Treated Within German Hodgkin's Study Group Trials J. Clin. Oncol., August 20, 2005; 23(24): 5739 - 5745. [Abstract] [Full Text] [PDF]

				A. Josting, L. Nogova, J. Franklin, J.-P. Glossmann, H. T. Eich, M. Sieber, T. Schober, H.-D. Boettcher, U. Schulz, R.-P. Muller, et al. Salvage Radiotherapy in Patients With Relapsed and Refractory Hodgkin's Lymphoma: A Retrospective Analysis From the German Hodgkin Lymphoma Study Group J. Clin. Oncol., March 1, 2005; 23(7): 1522 - 1529. [Abstract] [Full Text] [PDF]

				V. Ballova, J.-U. Ruffer, H. Haverkamp, B. Pfistner, H. K. Muller-Hermelink, E. Duhmke, P. Worst, M. Wilhelmy, R. Naumann, M. Hentrich, et al. A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin's disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly) Ann. Onc., January 1, 2005; 16(1): 124 - 131. [Abstract] [Full Text] [PDF]

				B. D. Cheson What Is New in Lymphoma? CA Cancer J Clin, September 1, 2004; 54(5): 260 - 272. [Abstract] [Full Text] [PDF]

				A. Levis, A. P. Anselmo, A. Ambrosetti, F. Adamo, M. Bertini, E. Cavalieri, P. Gavarotti, A. Genua, M. Liberati, V. Pavone, et al. VEPEMB in elderly Hodgkin's lymphoma patients. Results from an Intergruppo Italiano Linfomi (IIL) study Ann. Onc., January 1, 2004; 15(1): 123 - 128. [Abstract] [Full Text] [PDF]

				P. Borchmann, J. F. Treml, H. Hansen, C. Gottstein, R. Schnell, O. Staak, H.-f. Zhang, T. Davis, T. Keler, V. Diehl, et al. The human anti-CD30 antibody 5F11 shows in vitro and in vivo activity against malignant lymphoma Blood, November 15, 2003; 102(10): 3737 - 3742. [Abstract] [Full Text] [PDF]

				P. Hartmann, U. Rehwald, B. Salzberger, C. Franzen, M. Sieber, A. Wohrmann, and V. Diehl BEACOPP therapeutic regimen for patients with Hodgkin's disease and HIV infection Ann. Onc., October 1, 2003; 14(10): 1562 - 1569. [Abstract] [Full Text] [PDF]

				J. M. Connors Hodgkin's Lymphoma: The Hazards of Success J. Clin. Oncol., September 15, 2003; 21(18): 3388 - 3390. [Full Text] [PDF]

				S. Hohaus, G. Massini, F. D'Alo', F. Guidi, R. Putzulu, A. Scardocci, A. Rabi, A. L. Di Febo, M. T. Voso, and G. Leone Association between Glutathione S-Transferase Genotypes and Hodgkin's Lymphoma Risk and Prognosis Clin. Cancer Res., August 1, 2003; 9(9): 3435 - 3440. [Abstract] [Full Text] [PDF]

				D. L. Longo Radiation Therapy in the Treatment of Hodgkin's Disease--Do You See What I See? J Natl Cancer Inst, July 2, 2003; 95(13): 928 - 929. [Full Text] [PDF]

				V. Diehl, J. Franklin, M. Pfreundschuh, B. Lathan, U. Paulus, D. Hasenclever, H. Tesch, R. Herrmann, B. Dorken, H.-K. Muller-Hermelink, et al. Standard and Increased-Dose BEACOPP Chemotherapy Compared with COPP-ABVD for Advanced Hodgkin's Disease N. Engl. J. Med., June 12, 2003; 348(24): 2386 - 2395. [Abstract] [Full Text] [PDF]

				B. M.P. Aleman, J. M.M. Raemaekers, U. Tirelli, R. Bortolus, M. B. van 't Veer, M. L.M. Lybeert, J. J. Keuning, P. Carde, T. Girinsky, R. W.M. van der Maazen, et al. Involved-Field Radiotherapy for Advanced Hodgkin's Lymphoma N. Engl. J. Med., June 12, 2003; 348(24): 2396 - 2406. [Abstract] [Full Text] [PDF]

				R. Schnell, P. Borchmann, J. O. Staak, J. Schindler, V. Ghetie, E. S. Vitetta, and A. Engert Clinical evaluation of ricin A-chain immunotoxins in patients with Hodgkin's lymphoma Ann. Onc., May 1, 2003; 14(5): 729 - 736. [Abstract] [Full Text] [PDF]

				M. Sieber, H. Bredenfeld, A. Josting, T. Reineke, U. Rueffer, T. Koch, R. Naumann, F. Boissevain, P. Koch, P. Worst, et al. 14-Day Variant of the Bleomycin, Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine, and Prednisone Regimen in Advanced-Stage Hodgkin's Lymphoma: Results of a Pilot Study of the German Hodgkin's Lymphoma Study Group J. Clin. Oncol., May 1, 2003; 21(9): 1734 - 1739. [Abstract] [Full Text] [PDF]

				V. Diehl Advanced Hodgkin's Disease: ABVD Is Better, Yet Is Not Good Enough! J. Clin. Oncol., February 15, 2003; 21(4): 583 - 585. [Full Text] [PDF]

				P. Borchmann, R. Schnell, I. Fuss, O. Manzke, T. Davis, L. D. Lewis, D. Behnke, C. Wickenhauser, P. Schiller, V. Diehl, et al. Phase 1 trial of the novel bispecific molecule H22xKi-4 in patients with refractory Hodgkin lymphoma Blood, October 16, 2002; 100(9): 3101 - 3107. [Abstract] [Full Text] [PDF]

				A. Josting, C. Rudolph, M. Reiser, M. Mapara, M. Sieber, H. H. Kirchner, B. Dorken, D. K. Hossfeld, V. Diehl, and A. Engert Time-intensified dexamethasone/cisplatin/cytarabine: an effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkin's disease Ann. Onc., October 1, 2002; 13(10): 1628 - 1635. [Abstract] [Full Text] [PDF]

				J. A. Radford, A. Z.S. Rohatiner, W. D.J. Ryder, D. P. Deakin, T. Barbui, N. P. Lucie, A. Rossi, D. J. Dunlop, R. A. Cowan, P. M. Wilkinson, et al. ChlVPP/EVA Hybrid Versus the Weekly VAPEC-B Regimen for Previously Untreated Hodgkin's Disease J. Clin. Oncol., July 1, 2002; 20(13): 2988 - 2994. [Abstract] [Full Text] [PDF]

				G. P. Canellos New Treatments for Advanced Hodgkin's Disease: An Uphill Fight Beginning Close to the Top J. Clin. Oncol., February 1, 2002; 20(3): 607 - 609. [Full Text] [PDF]

				S. J. Horning, R. T. Hoppe, S. Breslin, N. L. Bartlett, B. W. Brown, and S. A. Rosenberg Stanford V and Radiotherapy for Locally Extensive and Advanced Hodgkin's Disease: Mature Results of a Prospective Clinical Trial J. Clin. Oncol., February 1, 2002; 20(3): 630 - 637. [Abstract] [Full Text] [PDF]

				M. Sieber, H. Tesch, B. Pfistner, U. Rueffer, B. Lathan, O. Brosteanu, U. Paulus, T. Koch, M. Pfreundschuh, M. Loeffler, et al. Rapidly Alternating COPP/ABV/IMEP Is Not Superior to Conventional Alternating COPP/ABVD in Combination With Extended-Field Radiotherapy in Intermediate-Stage Hodgkin's Lymphoma: Final Results of the German Hodgkin's Lymphoma Study Group Trial HD5 J. Clin. Oncol., January 15, 2002; 20(2): 476 - 484. [Abstract] [Full Text] [PDF]

				A. Josting, J. Franklin, M. May, P. Koch, M. K. Beykirch, J. Heinz, C. Rudolph, V. Diehl, and A. Engert New Prognostic Score Based on Treatment Outcome of Patients With Relapsed Hodgkin's Lymphoma Registered in the Database of the German Hodgkin's Lymphoma Study Group J. Clin. Oncol., January 1, 2002; 20(1): 221 - 230. [Abstract] [Full Text] [PDF]

				A. Josting, U. Rueffer, J. Franklin, M. Sieber, V. Diehl, and A. Engert Prognostic factors and treatment outcome in primary progressive Hodgkin lymphoma: a report from the German Hodgkin Lymphoma Study Group Blood, August 15, 2000; 96(4): 1280 - 1286. [Abstract] [Full Text] [PDF]

				A. Santoro, H. Bredenfeld, L. Devizzi, H. Tesch, V. Bonfante, S. Viviani, F. Fiedler, H. S. Parra, C. Benoehr, M. Pacini, et al. Gemcitabine in the Treatment of Refractory Hodgkin's Disease: Results of a Multicenter Phase II Study J. Clin. Oncol., July 1, 2000; 18(13): 2615 - 2619. [Abstract] [Full Text] [PDF]

				S. J. Horning, J. Williams, N. L. Bartlett, J. M. Bennett, R. T. Hoppe, D. Neuberg, and P. Cassileth Assessment of the Stanford V Regimen and Consolidative Radiotherapy for Bulky and Advanced Hodgkin’s Disease: Eastern Cooperative Oncology Group Pilot Study E1492 J. Clin. Oncol., March 1, 2000; 18(5): 972 - 972. [Abstract] [Full Text] [PDF]