Hodgkin’s disease remains one of the few malignant diseases which can be cured by modern chemotherapy in most cases even in advanced stages. Adriamycin-containing chemotherapy regimens are considered as the standard therapy which induce long-term remission in about 60–70% of patients. The ABVD scheme, developed by Bonadonna and colleagues in Milan, has a favorable toxicity profile and causes less myelotoxicity, acute leukemia or sterility relative to many previous treatment programs containing alkylating agents. However, 20– 30 % of patients eventually relapse and are then frequently treated with high-dose programs including stem cell transplantation. There are two major goals in advanced Hodgkin’s disease: (1) to improve the cure rate and (2) to reduce acute and long-term toxicities. The recent definition of prognostic factors identified patients who are at a high risk of treatment failure as well as those in whom less toxic approaches can be applied. The optimal approach or program has not yet been defined, although new chemotherapy regimens such as BEACOPP and Stanford V with increased tumor response rates have been identified. These new drug combinations are currently analyzed and compared with ABVD in several international trials. While the addition of radiotherapy improved disease control in some trials a survival benefit was not identified and the role of radiotherapy remains controversial. High dose programs remain experimental in advanced stage Hodgkin’s disease and should be restricted to prospective clinical trials.

Skipper HE, Schabel FM, Wilcox WS: Experimental evaluation of potential anticancer agents. XIII. On the criteria and kinetics associated with ‘curability’ of experimental leukemia. Cancer Chemother Rep 1964;35:1–11.
De Vita VT, Serpick A: Combination chemotherapy in the treatment of advanced Hodgkin’s disease. Proc Am Assoc Cancer Res 1967;8:13.
DeVita VJ, Hubbard SM: Hodgkin’s disease. N Engl J Med 1993;328:560–565.
Longo D, Young R, Wesley M, Hubbard S, Duffey P, Jaffe E, De VVJ: Twenty years of MOPP therapy for Hodgkin’s disease. J Clin Oncol 1986;4:1295–1306.
Bonadonna G, Valagussa P, Santoro A: Alternating non-cross-resistant combination chemotherapy or MOPP in stage IV Hodgkin’s disease. A report of 8-year results. Ann Intern Med 1986;104:739–746.
Nissen NI, Pajak TF, Glidewell O: A comparative study of a BCNU containing 4-drug program versus MOPP versus 3-drug combinations in advanced Hodgkin’s disease: A cooperative study by the Cancer and Leukemia Group B. Cancer 1979;43:31–40.
Bakemeier R, Anderson J, Costello W, Rosner G, Horton J, Glick J, Hines J, Berard C, DeVita VT Jr: BCVPP chemotherapy for advanced Hodgkin’s disease: Evidence for greater duration of complete remission, greater survival, and less toxicity than with a MOPP regimen. Results of the Eastern Cooperative Oncology Group study. Ann Intern Med 1984;101:447–456.
Nicholson WM, Beard ME, Crowther D: Combination chemotherapy in generalized Hodgkin’s disease. Br Med J 1970;iii: 7–10.
Sutcliffe SB, Wrigley PF, Peto J: MVPP chemotherapy regimen for advanced Hodgkin’s disease. Br Med J 1978;i:679–683.
Hancock B: Randomised study of MOPP (mustine, Oncovin, procarbazine, prednisone) against LOPP (Leukeran substituted for mustine) in advanced Hodgkin’s disease. British National Lymphoma Investigation. Radiother Oncol 1986;7:215–221.
Bonadonna G, Zucali R, Monfardini S, De Lena M, Uslenghi C: Combination chemotherapy of Hodgkin’s disease with Adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP. Cancer 1975;36:252–259.
Santoro A, Bonadonna G, Valagussa P: Long-term results of combined chemotherapy-radiotherapy approach in Hodgkin’s disease: Superiority of ABVD plus radiotherapy versus MOPP plus radiotherapy. J Clin Oncol 1987;5:27–37.
Canellos GP, Anderson JR, Propert KJ: Chemotherapy of advanced Hodgkin’s disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med 1992;327:1478–1484.
Somers R, Carde P, Henry-Amar M, Tarayre M, Thomas J, Hagenbeek A, Monconduit M, de Pauw BE, Breed W, Verdonck L, et al: A randomized study in stage IIIB and IV Hodgkin’s disease comparing eight courses of MOPP versus an alteration of MOPP with ABVD: A European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group and Groupe Pierre-et-Marie-Curie controlled clinical trial. J Clin Oncol 1994;12:279–287.
DeVita VJ, Simon RM, Hubbard SM: Curability of advanced Hodgkin’s disease with chemotherapy. Long-term follow-up of MOPP-treated patients at the National Cancer Institute. Ann Intern Med 1980;92:587–595.
Canellos G, Anderson J, Propert K, Nissen N, Cooper M, Henderson E, Green M, Gottlieb A, Peterson B: Chemotherapy of advanced Hodgkin’s disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med 1992;327:1478–1484.
Goldie JH, Coldman AJ: A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep 1979;63:1727–1733.
Jones S, Haut A, Weick J, Wilson H, Grozea P, Fabian C, McKelvey E, Byrne GJ, Hartsock R, Dixon D, Coltman CJ: Comparison of Adriamycin-containing chemotherapy (MOP-BAP) with MOPP-bleomycin in the management of advanced Hodgkin’s disease. A Southwest Oncology Group Study. Cancer 1983;51:1339–1347.
Viviani S, Bonadonna G, Santoro A, Bonfante V, Zanini M, Devizzi L, Soncini F, Valagussa P: Alternating versus hybrid MOPP and ABVD combinations in advanced Hodgkin’s disease: Ten-year results. J Clin Oncol 1996;14:1421–1430.
Sieber M, Rueffer U, Tesch H: Rapidly alternating COPP + ABV + IMEP (CAI) is equally effective as alternating COPP + ABVD (CA) for Hodgkin’s disease: Final results of two randomised trials for intermediate (HD5 protocol) and advanced (HD6 protocol) stages. Leuk Lymphoma 1998;12:132–138.
Schmoll H: Review of etoposide single-agent activity. Cancer Treat Rev 1982;9:21–30.
Horning SJ, Rosenberg SA, Hoppe RT: Brief chemotherapy (Stanford V) and adjuvant radiotherapy for bulky or advanced Hodgkin’s disease: An update. Ann Oncol 1996;7:105–108.
Radford JA, Rohatiner AZS, Dunlop DJ: Preliminary results of a four-centre randomised trial comparing weekly VAPEC-B chemotherapy with the ChlVPP/EVA hybrid regimen in previously untreated patients. Proc Am Soc Clin Oncol 1997;16:12.
Carde P, MacKintosh F, Rosenberg S: A dose and time response analysis of the treatment of Hodgkin’s disease with MOPP chemotherapy. J Clin Oncol 1983;1:146–153.
Gerhartz HH, Schwencke H, Bazarbashi S: Randomized comparison of COPP/ABVD vs. dose and time-escalated COPP/ABVD with GM-CSF support for advanced Hodgkin’s disease. Blood 1997;90:389–396.
Hasenclever D, Loeffler M, Diehl V: Rationale for dose escalation of first line conventional chemotherapy in advanced Hodgkin’s disease. German Hodgkin’s Lymphoma Study Group. Ann Oncol 1996;7(suppl 4):95–98.
Diehl V: Dose-escalation study for the treatment of Hodgkin’s disease. The German Hodgkin Study Group (GHSG). Ann Hematol 1993;66:139–140.
Diehl V, Franklin J, Hasenclever D, Tesch H, Pfreundschuh M, Lathan B, Paulus U, Sieber M, Ruffer J, Sextro M, Engert A, Wolf J, Hermann R, Holmer L, Stappert-Jahn U, Winnerlein-Trump E, Wulf G, Krause S, Glunz A, von Kalle K, Bischoff H, Haedicke C, Duhmke E, Georgii A, Loeffler M: BEACOPP: A new regimen for advanced Hodgkin’s disease. German Hodgkin’s Lymphoma Study Group. Ann Oncol 1998;9(suppl 5):67–71.
Diehl V, Franklin J, Hasenclever D, Tesch H, Pfreundschuh M, Lathan B, Paulus U, Sieber M, Rueffer J, Sextro M, Engert A, Wolf J, Hermann R, Holmer L, Stappert-Jahn U, Winnerlein-Trump E, Wulf G, Krause S, Glunz A, von Kalle K, Bischoff H, Haedicke C, Duehmke E, Georgii A, Loeffler M: 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. J Clin Oncol 1998;16:3810–3821.
Chopra R, McMillan A, Linch D, Yuklea S, Taghipour G, Pearce R, Patterson K, Goldstone A: The place of high-dose BEAM therapy and autologous bone marrow transplantation in poor-risk Hodgkin’s disease. A single-center eight-year study of 155 patients. Blood 1993;81:1137–1145.
Horning S, Chao N, Negrin R, Hoppe R, Long G, Hu W, Wong R, Brown B, Blume K: High-dose therapy and autologous hematopoietic progenitor cell transplantation for recurrent or refractory Hodgkin’s disease: Analysis of the Stanford University results and prognostic indices. Blood 1997;89:801–813.
Reece D, Phillips G: Intensive therapy and autologous stem cell transplantation for Hodgkin’s disease in first relapse after combination chemotherapy. Leuk Lymphoma 1996;21:245–253.
Carella A, Carlier P, Congiu A, Occhini D, Nati S, Santini G, Pierluigi D, Giordano D, Bacigalupo A, Damasio E: Autologous bone marrow transplantation as adjuvant treatment for high-risk Hodgkin’s disease in first complete remission after MOPP/ABVD protocol. Bone Marrow Transplant 1991;8:99–103.
Straus D, Gaynor J, Myers J, Merke D, Caravelli J, Chapman D, Yahalom J, Clarkson B: Prognostic factors among 185 adults with newly diagnosed advanced Hodgkin’s disease treated with alternating potentially non-cross-resistant chemotherapy and intermediate-dose radiation therapy. J Clin Oncol 1990;8:1173–1186.
Proctor S, Taylor P, Mackie M, Donnan P, Boys R, Lennard A, Prescott R: A numerical prognostic index for clinical use in identification of poor-risk patients with Hodgkin’s disease at diagnosis. The Scotland and Newcastle Lymphoma Group (SNLG) Therapy Working Party. Leuk Lymphoma 1992;7(suppl):17–20.
Goldstone A: The case for and against high-dose therapy with stem cell rescue for early poor prognosis Hodgkin’s disease in first remission. Ann Oncol 1998;9(suppl 5):83–85.
Hasenclever D, Schmitz N, Diehl V: Is there a rationale for high-dose chemotherapy as first line treatment of advanced Hodgkin’s disease? German Hodgkin’s Lymphoma Study Group (GHSG). Leuk Lymphoma 1995;15(suppl 1): 47–49.
Hasenclever D, Diehl V: A prognostic score for advanced Hodgkin’s disease. International Prognostic Factors Project on Advanced Hodgkin’s Disease. N Engl J Med 1998;339:1506–1514.
Kinzie J, Hanks G, MacLean C, Kramer S: Patterns of care study: Hodgkin’s disease relapse rates and adequacy of portals. Cancer 1983;52:2223–2226.
Fabian C, Mansfield C, Dahlberg S, Jones S, Miller T, Van Slyck E, Grozea P, Morrison F, Coltman CJ, Fisher R: Low-dose involved field radiation after chemotherapy in advanced Hodgkin disease. A Southwest Oncology Group randomized study. Ann Intern Med 1994;120:903–912.
Diehl V, Loeffler M, Pfreundschuh M, Ruehl U, Hasenclever D, Nisters-Backes H, Sieber M, Smith K, Tesch H, Geilen W, et al: Further chemotherapy versus low-dose involved-field radiotherapy as consolidation of complete remission after six cycles of alternating chemotherapy in patients with advance Hodgkin’s disease. German Hodgkin’s Study Group (GHSG). Ann Oncol 1995;6:901–910.
Loeffler M, Brosteanu O, Hasenclever D, Sextro M, Assouline D, Bartolucci A, Cassileth P, Crowther D, Diehl V, Fisher R, Hoppe R, Jacobs P, Pater J, Pavlovsky S, Thompson E, Wiernik P: Meta-analysis of chemotherapy versus combined modality treatment trials in Hodgkin’s disease. International Database on Hodgkin’s Disease Overview Study Group. J Clin Oncol 1998;16:818–829.
Raemaekers J, Burgers M, Henry-Amar M, Pinna A, Mandard A, Monfardini S, Hagenbeek A, Breed W, Carde P, Vovk M, van Hoof A, Thomas J, Noordijk E: Patients with stage III/IV Hodgkin’s disease in partial remission after MOPP/ABV chemotherapy have excellent prognosis after additional involved-field radiotherapy: Interim results from the ongoing EORTC-LCG and GPMC phase III trial. The EORTC Lymphoma Cooperative Group and Groupe Pierre-et-Marie-Curie. Ann Oncol 1997;8(suppl 1):111–114.
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