Current Hematologic Malignancy Reports

, Volume 1, Issue 1, pp 51–59

First-line treatment of Hodgkin’s lymphoma

Article

Abstract

Substantial clinical progress over the last decades has made Hodgkin’s lymphoma into one of the most curable human cancers in adults. About 80% of patients in all stages and of all histologic subtypes experience long-term disease-free survival. Modern treatment strategies aim to improve chemotherapy and radiotherapy, while minimizing therapy-related toxicities. Ongoing trials investigate a reduction of chemotherapy doses or cycles and the application of lower radiation doses and smaller radiation field sizes. For patients with a specific high-risk profile, novel approaches with more intense drug combinations are currently being investigated in clinical trials. This review discusses recent approaches to the first-line treatment of early-favorable, early-unfavorable, and advanced-stage Hodgkin’s lymphoma.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Harris NL, Jaffe ES, Diebold J, et al.: The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November, 1997. Ann Oncol 1999, 10:1419–1432.PubMedCrossRefGoogle Scholar
  2. 2.
    Lister T, Crowther D, Sutcliffe S, et al.: Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin’s disease: Cotswolds meeting. J Clin Oncol 1989, 7:1630–1636.PubMedGoogle Scholar
  3. 3.
    Diehl V, Stein H, Hummel M, et al.: Hodgkin’s lymphoma: biology and treatment strategies for primary, refractory, and relapsed disease. Hematology [Am Soc Hematol Educ Program] 2003, 225–472. A comprehensive and timely intergroup review on the biology and treatment of HL.Google Scholar
  4. 4.
    Hasenclever D, Diehl V, Armitage JO, et al. for the International Prognostic Factors Project on Advanced Hodgkin’s Disease: A prognostic score for advanced Hodgkin’s disease. N Engl J Med 1998, 339:1506–1514.PubMedCrossRefGoogle Scholar
  5. 5.
    Kaplan HS: Evidence for a tumoricidal dose level in the radiotherapy of Hodgkin’s disease. Cancer Res 1966, 26:1221–1224.PubMedGoogle Scholar
  6. 6.
    Horwich A, Specht L, Ashley S: Survival analysis of patients with clinical stages I or II Hodgkin’s disease who have relapsed after initial treatment with radiotherapy alone. Eur J Cancer 1997, 33:848–853.PubMedCrossRefGoogle Scholar
  7. 7.
    Specht L, Gray RG, Clarke MJ, et al.: Influence of more extensive radiotherapy and adjuvant chemotherapy on long-term outcome of early-stage Hodgkin’s disease: a meta-analysis of 23 randomized trials involving 3888 patients. International Hodgkin’s Disease Collaborative Group. J Clin Oncol 1998, 16:830–843.PubMedGoogle Scholar
  8. 8.
    Hancock SL, Tucker MA, Hoppe RT: Factors affecting late mortality from heart disease after treatment of Hodgkin’s disease. JAMA 1993, 270:1949–1955.PubMedCrossRefGoogle Scholar
  9. 9.
    Dubray B, Henry-Amar M, Meerwaldt JH, et al.: Radiation-induced lung damage after thoracic irradiation for Hodgkin’s disease: the role of fractionation. Radiother Oncol 1995, 36:211–217.PubMedCrossRefGoogle Scholar
  10. 10.
    Hancock SL, Cox RS, McDougall IR: Thyroid diseases after treatment of Hodgkin’s disease. N Engl J Med 1991, 325:599–605.PubMedCrossRefGoogle Scholar
  11. 11.
    van Leeuwen FE, Klokman WJ, Veer MB, et al.: Long-term risk of second malignancy in survivors of Hodgkin’s disease treated during adolescence or young adulthood. J Clin Oncol 2000, 18:487–497.PubMedGoogle Scholar
  12. 12.
    Ng AK, Bernardo MV, Weller E, et al.: Second malignancy after Hodgkin’s disease treated with radiation therapy with or without chemotherapy: long-term risks and risk factors. Blood 2002, 100:1989–1996.PubMedCrossRefGoogle Scholar
  13. 13.
    Bhatia S, Yasui Y, Robison LL, et al.: High risk of subsequent neoplasms continues with extended follow-up of childhood Hodgkin’s disease: report from the Late Effects Study Group. J Clin Oncol 2003, 21:4386–4394.PubMedCrossRefGoogle Scholar
  14. 14.
    van Leeuwen FE, Klokman WJ, Stovall M, et al.: Roles of radiation dose, chemotherapy, and hormonal factors in breast cancer following Hodgkin’s disease. J Natl Cancer Inst 2003, 95:971–980.PubMedCrossRefGoogle Scholar
  15. 15.
    Behringer K, Josting A, Schiller P, et al.: Solid tumors in patients treated for Hodgkin’s disease: a report from the German Hodgkin Lymphoma Study Group. Ann Oncol 2004, 15:1079–1085.PubMedCrossRefGoogle Scholar
  16. 16.
    Biti GP, Cimino G, Cartoni C, et al.: Extended-field radiotherapy is superior to MOPP chemotherapy for the treatment of pathologic stage I-IIA Hodgkin’s disease: eight-year update of an Italian prospective randomized study. J Clin Oncol 1992, 10:378–382.PubMedGoogle Scholar
  17. 17.
    Press OW, LeBlanc M, Lichter AS, et al.: Phase III randomized intergroup trial of subtotal lymphoid irradiation versus doxorubicin, vinblastine, and subtotal lymphoid irradiation for stage IA to IIA Hodgkin’s disease. J Clin Oncol 2001, 19:4238–4244.PubMedGoogle Scholar
  18. 18.
    Horning SJ, Hoppe RT, Breslin S, et al.: Very brief (8 week) chemotherapy (CT) and low dose (30 Gy) radiotherapy (RT) for limited stage Hodgkin’s disease (dHD): preliminary results of the Stanford-Kaiser G4 study of Stanford V + RT [abstract]. Blood 1999, 94:1717a.Google Scholar
  19. 19.
    Bonfante V, Viviani S, Devizz IL, et al.: Ten-year experience with ABVD plus radiotherapy: subtotal nodal (STNI) versus involved field (IFRT) in early stage Hodgkin’s disease [abstract]. Proc ACSO 2001, 20:281a, Abstract 1120.Google Scholar
  20. 20.
    Raemaekers J, Kluin-Nelemans H, Teodorovic I, et al.: The achievements of the EORTC Lymphoma Group. European Organisation for Research and Treatment of Cancer. Eur J Cancer 2002, 38:S107-S113. Brief but very informative overview of all lymphoma trials conducted by the EORTC, providing the background, aims, and results of former trials and the design and strategies of currently open trials.PubMedCrossRefGoogle Scholar
  21. 21.
    Sieber M, Franklin J, Tesch H, et al.: Two cycles ABVD plus extended field radiotherapy is superior to radiotherapy alone in early stage Hodgkin’s disease: Results of the German Hodgkin’s Lymphoma Study Group (GHSG) Trial HD7. Blood 2002, 100:341a.CrossRefGoogle Scholar
  22. 22.
    Ekstrand BC, Lucas JB, Horwitz SM, et al.: Rituximab in lymphocyte-predominant Hodgkin disease: results of a phase 2 trial. Blood 2003, 101:4285–4289.PubMedCrossRefGoogle Scholar
  23. 23.
    Rehwald U, Schulz H, Reiser M, et al.: Treatment of relapsed CD20+ Hodgkin lymphoma with the monoclonal antibody rituximab is effective and well tolerated: results of a phase II trial of the German Hodgkin Lymphoma Study Group. Blood 2003, 101:420–424.PubMedCrossRefGoogle Scholar
  24. 24.
    Bonadonna G, Zucali R, Monfardini S, et al.: Combination chemotherapy of Hodgkin’s disease with adriamycin, bleomycin, vinblastine, and imidazole carboximide versus MOPP. Cancer 1975, 36:252–259.PubMedCrossRefGoogle Scholar
  25. 25.
    Connors JM, Klimo P, Adams G, et al.: Treatment of advanced Hodgkin’s disease with chemotherapy—comparison of MOPP/ABV hybrid regimen with alternating courses of MOPP and ABVD: A report from the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 1997, 15:1638–1645.PubMedGoogle Scholar
  26. 26.
    Duggan DB, Petroni GR, Johnson JL, et al.: Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin’s disease: report of an intergroup trial. J Clin Oncol 2003, 21:607–614.PubMedCrossRefGoogle Scholar
  27. 27.
    Sieber M, Tesch H, Pfistner B, 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 2002, 20:476–484.PubMedCrossRefGoogle Scholar
  28. 28.
    Canellos GP, Anderson JR, Propert KJ, et al.: Chemotherapy of advanced Hodgkin’s disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med 1992, 327:1478–1484.PubMedCrossRefGoogle Scholar
  29. 29.
    Zittoun R, Audebert A, Hoerni B, et al.: Extended versus involved fields irradiation combined with MOPP chemotherapy in early clinical stages of Hodgkin’s disease. J Clin Oncol 1985, 3:207–214.PubMedGoogle Scholar
  30. 30.
    Engert A, Schiller P, Josting A, et al.: Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin’s lymphoma: Results of the HD8 trial of the German Hodgkin’s Lymphoma Study Group. J Clin Oncol 2003, 21:3601–3608. Final results of the largest randomized study demonstrating involved-field radiotherapy to be as effective as extended-field radiotherapy in the treatment of early-stage HL.PubMedCrossRefGoogle Scholar
  31. 31.
    Ferme C, Eghbali H, Habenbeek A, et al.: Mechlorethamine + vincristine + procarbazine + prednisone (MOPP/ABV-M/ A) hybrid and irradiation in unfavorable supradiaphragmatic clinical stages I-II HD: Comparison of three treatment modalities, preliminary results of the EORTCGELA H8-U randomized trial in 995 patients. Blood 2000, 96:576a.Google Scholar
  32. 32.
    Diehl V, Franklin J, Pfreundschuh M, et al.: Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin’s disease. N Engl J Med 2003, 348:2386–2395. Final analysis of a large randomized trial showing an excellent and superior outcome of patients treated with the new BEACOPP regimen compared to COPP+ABVD for advanced-stage HL.PubMedCrossRefGoogle Scholar
  33. 33.
    DeVita V T Jr, Hubbard SM: Hodgkin’s disease. N Engl J Med 1993, 328:560–565.PubMedCrossRefGoogle Scholar
  34. 34.
    Longo DL, Young RC, Wesley M, et al.: Twenty years of MOPP chemotherapy for Hodgkin’s disease. J Clin Oncol 1986, 4:1295–1306.PubMedGoogle Scholar
  35. 35.
    Bonadonna G, Valagussa P, Santoro A: Alternating noncross-resistant combination chemotherapy or MOPP in stage IV Hodgkin’s disease. A report of 8-year results. Ann Intern Med 1986, 104:739–746.PubMedGoogle Scholar
  36. 36.
    Hancock BW: Randomised study of MOPP against LOPP in advanced Hodgkin’s disease. British National Lymphoma Investigation. Radiother Oncol 1986, 7:215–221.PubMedCrossRefGoogle Scholar
  37. 37.
    Santoro J, Bonadonna G, Valagussa P, et al.: 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.PubMedGoogle Scholar
  38. 38.
    Sieber M, Tesch H, Pfistner B, et al.: Treatment of advanced Hodgkin’s disease with COPP/ABV/IMEP versus COPP/ ABVD and consolidating radiotherapy: final results of the German Hodgkin’s Lymphoma Study Group HD6 trial. Ann Oncol 2004, 15:276–282.PubMedCrossRefGoogle Scholar
  39. 39.
    Canellos GP, Niedzwiecki D: Long-term follow-up of Hodgkin’s disease trial. N Engl J Med 2002, 346:1417–1418.PubMedCrossRefGoogle Scholar
  40. 40.
    Horning SJ, Hoppe RT, Breslin S, et al.: Stanford V and radiotherapy for locally extensive and advanced Hodgkin’s disease: mature results of a prospective clinical trial. J Clin Oncol 2002, 20:630–637. Demonstration that high cure rates can be achieved with the novel regimen Stanford V in early-unfavorable and advanced-stage HL.PubMedCrossRefGoogle Scholar
  41. 41.
    Chisesi T, Federico M, Levis A, et al.: ABVD versus Stanford V versus MEC in unfavourable Hodgkin’s lymphoma: results of a randomised trial. Ann Oncol 2002, 13(Suppl 1):102–106.PubMedGoogle Scholar
  42. 42.
    Radford JA, Rohatiner AZ, Ryder WD, et al.: ChlVPP/EVA hybrid versus the weekly VAPEC-B regimen for previously untreated Hodgkin’s disease. J Clin Oncol 2002, 20:2988–2994.PubMedCrossRefGoogle Scholar
  43. 43.
    Sieber M, Bredenfeld H, Josting A, 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 2003, 21:1734–1739.PubMedCrossRefGoogle Scholar
  44. 44.
    Josting A, Wiedenmann S, Franklin J, et al.: Secondary myeloid leukemia and myelodysplastic syndromes in patients treated for Hodgkin’s disease: a report from the German Hodgkin’s Lymphoma Study Group. J Clin Oncol 2003, 21:3440–3446.PubMedCrossRefGoogle Scholar
  45. 45.
    Bredenfeld H, Franklin J, Nogov’a L, et al.: Severe pulmonary toxicity in patients with advanced-stage Hodgkin’s disease treated with a BEACOPP regimen is probably related to the combination of gemcitabine and bleomycin: a report of the German Hodgkin’s Lymphoma Study Group. J Clin Oncol 2004, 22:2424–2429.PubMedCrossRefGoogle Scholar
  46. 46.
    Federico M, Bellei M, Brice P, et al.: High-dose therapy and autologous stem-cell transplantation versus conventional therapy for patients with advanced Hodgkin’s lymphoma responding to front-line therapy. J Clin Oncol 2003, 21:2320–2325.PubMedCrossRefGoogle Scholar
  47. 47.
    Aleman BM, Raemaekers JM, Tirelli U, et al.: Involvedfield radiotherapy for advanced Hodgkin’s lymphoma. N Engl J Med 2003, 348:2396–2406. Results of a randomized comparison showing that consolidating radiotherapy to the involved field is unnecessary for patients with advanced-stage HL who achieve complete remission after six to eight cycles of effective chemotherapy.PubMedCrossRefGoogle Scholar
  48. 48.
    Löffler M, Brosteanu O, Hasenclever D, et al.: Meta-analysis of chemotherapy versus combined modality treatment trials in Hodgkin’s disease. J Clin Oncol 1998, 16:818–829.Google Scholar
  49. 49.
    Kreuser ED, Felsenberg D, Behles C, et al.: Long-term gonadal dysfunction and its impact on bone mineralization in patients following COPP/ABVD chemotherapy for Hodgkin’s disease. Ann Oncol 1992, 3(Suppl 4):105–110.PubMedGoogle Scholar
  50. 50.
    Blumenfeld Z, Dann E, Avivi I, et al.: Fertility after treatment for Hodgkin’s disease. Ann Oncol 2002, 13(Suppl 1):38–147.Google Scholar

Copyright information

© Current Science Inc 2006

Authors and Affiliations

  1. 1.First Department of Internal MedicineUniversity Hospital CologneCologneGermany

Personalised recommendations