EDITORIAL

www.nature.com/clinicalpractice/onc Will it be another 20 years before Hodgkin patients benefit from BEACOPP therapy? Volker Diehl and Andreas Engert

Hodgkin lymphoma (HL) has become one of Let us hope The , , , cyclo- the most curable malignancies in adults. Major it will not phosphamide, , , and success was achieved by vigorous improvement prednisone (BEACOPP) regimen, developed by in radiation techniques and, more importantly, take another the German Hodgkin Study Group (GHSG), chal- by the development of multiagent polychemo- 20 years until lenged ABVD as standard therapy for patients therapy. In the late 1960s, DeVita and coworkers all patients can with advanced HL. In the prospectively random- were the first to pioneer the combination of benefit from ized three-arm HD9 study of the GHSG, two mechlorethamine, vincristine, procarbazine this medical BEACOPP regimens (dose-escalated and stan- and prednisone (MOPP)—one of the landmark dard) were compared with the cyclophospha- events in modern .1 When this regimen progress. mide, vincristine, procarbazine, and prednisone was used in patients with advanced HL, more (COPP)/ABVD regimen. This trial included 1,186 than 80% achieved remission, with approxi- patients, 466 of whom were treated with dose- mately 50% alive at 5 years. In an attempt to escalated BEACOPP. The overall and tumor- find a non-crossresistant regimen, Bonadonna free survival at 5 years for patients treated with et al.2 developed an approach using doxorubicin, dose-escalated BEACOPP were 91% and 87%, bleomycin, , and (ABVD), respectively.3 After a 7-year follow-up period which had an improved antitumor efficacy and the superiority of dose-escalated BEACOPP in tolerability compared with MOPP. ABVD was terms of freedom from treatment failure (85% initially regarded as ‘European’ in contrast to the versus 75% versus 67%) and overall survival US-developed MOPP. Surprisingly, it took nearly (90% versus 84% versus 79%) was clearly 20 years before ABVD finally replaced MOPP demonstrated. The overall treatment-associated or MOPP-like regimens for the treatment of mortality was also lower with this regimen. advanced HL. This was partly because the effi- Death caused by progressive HL was consider- cacy differences between these regimens were ably lower for dose-escalated BEACOPP (1.7%) subtle, with 5-year overall survival of around compared with COPP/ABVD (8.7%). The fact 80% and 70%, and tumor-free survival of 60% that more than 400 centers contributed to this and 50%, for ABVD and MOPP, respectively. trial, including community hospitals and more ABVD produced less short-term and long-term than 100 private oncologists, supports the broad toxicity, and is generally considered the ‘gold applicability of this regimen. standard’ for the treatment of advanced HL. Will the initial benefit in tumor control Experimental models and clinical practice observed with dose-escalated BEACOPP be V Diehl is an Advisory experience has shown HL to be extremely sensi- Board member of lost by a higher rate of late side-effects with tive to . Consequently, numerous Nature Clinical the more-aggressive drug combination? The clinical trials were designed with hybrid regimens Practice Oncology and reported 18% tumor-free survival difference at of MOPP and ABVD or variations incorporating A Engert is Secretary 7 years’ follow-up strongly suggests otherwise. up to 12 different drugs. These so-called ‘second of the GHSG and a It is noteworthy that after 7 years’ follow-up, the generation’ attempts did not result in better Senior Consultant patients treated with dose-escalated BEACOPP disease control, and showed that single-drug in Department I show statistically significant improvements in efficacy and drug intensity (i.e. dose over time) of Internal Medicine overall survival compared with those receiving are more important than the number of drugs at the University standard BEACOPP or ABVD. These results Hospital Cologne, given. With this knowledge, third-generation Germany. should influence working practices, including regimens were developed based on the ratio- those of primary-care specialists. Let us hope nale of using the putatively most effective drugs Competing interests it will not take another 20 years until all patients in the shortest time possible. Reducing the The authors declared can benefit from this medical progress. they have no competing dose intervals became possible with the avail- interests. ability of hematopoetic growth factors such as Supplementary information is available on the www.nature.com/clinicalpractice granulocyte colony-stimulating factor. doi:10.1038/ncponc0508 Nature Clinical Practice Oncology website.

MAY 2006 VOL 3 NO 5 NATURE CLINICAL PRACTICE ONCOLOGY 227

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