Current Clinical Trials

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Drug combinations described in this section:

• ABV: doxorubicin plus bleomycin plus vinblastine.
• ABVD: doxorubicin plus bleomycin plus vinblastine plus dacarbazine (1 cycle = 1 month of therapy).
• AV: doxorubicin plus vinblastine.
• AVD: doxorubicin plus vinblastine plus dacarbazine.
• MOPP-ABV: mechlorethamine plus vincristine plus procarbazine plus prednisone plus doxorubicin plus bleomycin plus vincristine.

Patients are designated as having early favorable Hodgkin lymphoma (HL) if they have clinical stage I or stage II disease and no adverse risk factors. Adverse risk factors include:

• B symptoms (fever ≥38°C, soaking night sweats, weight loss ≥10% within 6 months). (Refer to the PDQ summary on Fever, Sweats, and Hot Flashes for more information.)
• Extranodal disease.
• Bulky disease (≥10 cm or >33% of the chest diameter on chest x-ray).
• Three or more sites of nodal involvement.
• Sedimentation rate of 50 or more.

Historically, radiation therapy alone had been the primary treatment for patients with early favorable HL, often after confirmatory negative staging laparotomy. A randomized prospective trial involving 542 patients with early favorable HL compared MOPP-ABV for three cycles plus involved-field radiation therapy (IF-XRT) with subtotal nodal radiation; with a median follow-up of 7.7 years, combined modality was favored in terms of 5-year event-free survival (98% vs. 74%, P < .001) and 10-year overall survival (97% vs. 92%, P = .001).[1][Level of evidence: 1iiA] The late mortality from solid tumors, especially in the lung, breast, gastrointestinal tract, and connective tissue, and from cardiovascular disease makes radiation therapy a less attractive option for the best-risk patients, who have the highest probability of cure and long-term survival.[2-6] Recent clinical trials have focused on regimens with chemotherapy and IF-XRT or with chemotherapy alone.

A randomized prospective trial from the National Cancer Institute of Canada involving 123 patients with early favorable HL compared ABVD for four to six cycles to subtotal nodal radiation; with a median follow-up of 4.2 years, no difference was observed in event-free survival (88% vs. 87%; P = .60) or in overall survival (OS) (97% vs. 100%; P = .30).[7][Level of evidence: 1iiA]

In a randomized study from the Milan Cancer Institute of patients with clinical early-stage HL, 4 months of ABVD followed by either IF-XRT or extended-field radiation (EF-XRT) showed similar OS and freedom-from-progression with a 10-year median follow-up, but the study had inadequate statistical power to determine noninferiority of IF-XRT versus EF-XRT.[8][Level of evidence: 1iiDii]

The German Hodgkin Lymphoma Study Group (GHSG) randomly assigned 1,131 patients with early favorable HL to:

• Two cycles of ABVD plus 30 Gy of IF-XRT.
• Two cycles of ABVD plus 20 Gy of IF-XRT.
• Four cycles of ABVD plus 30 Gy of IF-XRT.
• Four cycles of ABVD plus 20 Gy of IF-XRT.

With a 3-year median follow-up, in a preliminary report in abstract form, no differences were observed in freedom-from-progression (97%) or OS (98%) for all four groups.[9][Level of evidence: 1iiA]

The ongoing GHSG study is comparing reduced chemotherapy schedules while maintaining IF-XRT at 30 Gy: two cycles of ABVD, two cycles of ABV, two cycles of AVD, or two cycles of AV.

A specialized approach to therapy can be taken when patients with nonbulky lymphocyte–predominant disease presenting in unilateral high neck (above the thyroid notch) or epitrochlear locations require only IF-XRT after clinical staging.[10] A retrospective report of 426 cases of lymphocyte-predominant HL (including the so-called nodular lymphocyte–predominant and lymphocyte-rich classical subtypes) showed that more patients died of treatment-related toxicity (both acute and long-term) than from recurrence of HL.[11][Level of evidence: 3iiiA] Limitation of radiation dose and radiation fields and avoidance of leukemogenic chemotherapeutic agents, along with watchful waiting policies, should be investigated for these subgroups.[12] Patients with nonbulky nodular sclerosing disease presenting in the anterior mediastinum only after clinical staging also do well with mantle radiation alone.[13]

Treatment options:

• ABVD for four to six cycles.
• ABVD for two cycles plus IF-XRT (20 Gy or 30 Gy).
• Radiation therapy alone in special circumstances.[14]

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage I adult Hodgkin lymphoma and stage II adult Hodgkin lymphoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1. Fermé C, Eghbali H, Meerwaldt JH, et al.: Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med 357 (19): 1916-27, 2007.  [PUBMED Abstract]
   
   
2. Dores GM, Metayer C, Curtis RE, et al.: Second malignant neoplasms among long-term survivors of Hodgkin's disease: a population-based evaluation over 25 years. J Clin Oncol 20 (16): 3484-94, 2002.  [PUBMED Abstract]
   
   
3. Reinders JG, Heijmen BJ, Olofsen-van Acht MJ, et al.: Ischemic heart disease after mantlefield irradiation for Hodgkin's disease in long-term follow-up. Radiother Oncol 51 (1): 35-42, 1999.  [PUBMED Abstract]
   
   
4. Longo DL: Radiation therapy in Hodgkin disease: why risk a Pyrrhic victory? J Natl Cancer Inst 97 (19): 1394-5, 2005.  [PUBMED Abstract]
   
   
5. Swerdlow AJ, Higgins CD, Smith P, et al.: Myocardial infarction mortality risk after treatment for Hodgkin disease: a collaborative British cohort study. J Natl Cancer Inst 99 (3): 206-14, 2007.  [PUBMED Abstract]
   
   
6. Engert A, Franklin J, Eich HT, et al.: Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin's lymphoma: final results of the GHSG HD7 trial. J Clin Oncol 25 (23): 3495-502, 2007.  [PUBMED Abstract]
   
   
7. Meyer RM, Gospodarowicz MK, Connors JM, et al.: Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group. J Clin Oncol 23 (21): 4634-42, 2005.  [PUBMED Abstract]
   
   
8. Bonadonna G, Bonfante V, Viviani S, et al.: ABVD plus subtotal nodal versus involved-field radiotherapy in early-stage Hodgkin's disease: long-term results. J Clin Oncol 22 (14): 2835-41, 2004.  [PUBMED Abstract]
   
   
9. Engert A, Pluetschow A, Eich H, et al.: Combined modality treatment of two or four cycles of ABVD followed by involved field radiotherapy in the treatment of patients with early stage Hodgkin's lymphoma: update interim analysis of the randomised HD10 study of the German Hodgkin Study Group. [Abstract] Blood 106: A-2673, 2005. 
   
   
10. Russell KJ, Hoppe RT, Colby TV, et al.: Lymphocyte predominant Hodgkin's disease: clinical presentation and results of treatment. Radiother Oncol 1 (3): 197-205, 1984.  [PUBMED Abstract]
    
    
11. Diehl V, Sextro M, Franklin J, et al.: Clinical presentation, course, and prognostic factors in lymphocyte-predominant Hodgkin's disease and lymphocyte-rich classical Hodgkin's disease: report from the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin's Disease. J Clin Oncol 17 (3): 776-83, 1999.  [PUBMED Abstract]
    
    
12. Aster JC: Lymphocyte-predominant Hodgkin's disease: how little therapy is enough? J Clin Oncol 17 (3): 744-6, 1999.  [PUBMED Abstract]
    
    
13. Backstrand KH, Ng AK, Takvorian RW, et al.: Results of a prospective trial of mantle irradiation alone for selected patients with early-stage Hodgkin's disease. J Clin Oncol 19 (3): 736-41, 2001.  [PUBMED Abstract]
    
    
14. Landgren O, Axdorph U, Fears TR, et al.: A population-based cohort study on early-stage Hodgkin lymphoma treated with radiotherapy alone: with special reference to older patients. Ann Oncol 17 (8): 1290-5, 2006.  [PUBMED Abstract]
    
    

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