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 ¹ for more information.)

Patients with stage I or contiguous stage II diffuse large B-cell lymphoma are candidates for combination chemotherapy with or without radiation therapy. Four prospective randomized trials have evaluated the comparison of CHOP (cyclophosphamide + doxorubicin + vincristine + prednisone) or more intensive CHOP-based chemotherapy alone versus combined modality therapy with CHOP and involved-field radiation therapy (IF-XRT).[1-5]

With 7 years' median follow-up, 576 patients older than 60 years with early-stage disease received four cycles of CHOP with or without IF-XRT; there was no difference in 5-year event-free survival (EFS) (61% vs. 64%, P = .5) or overall survival (OS)(72% vs. 68%, P = .6).[1][Level of evidence: 1iiA] A randomized trial of 401 patients comparing eight cycles of CHOP to three cycles of CHOP with IF-XRT was initially reported as having an OS advantage for the combined modality arm at 5 years, [2] but a re-evaluation for OS at 9 years showed no difference in either arm of the study.[3][Level of evidence: 1iiA] A randomized study (ECOG-1484 ²) of 210 patients who attained a radiologic complete remission after eight cycles of CHOP compared IF-XRT with no further therapy; there was no difference in OS at 10 years (68% vs. 65%, P = .24).[4][Level of evidence: 1iiA]

A randomized trial of 631 patients younger than 60 years compared more intensive CHOP-based chemotherapy versus three cycles of CHOP with IF-XRT; with 4 years' median follow-up, the intensive chemotherapy was superior in 5-year EFS (82% vs. 74%, P > .001) and 5-year OS (90% vs. 81%, P = .001).[5][Level of evidence: 1iiA]

The confirmation of efficacy for rituximab in advanced-stage disease as evidenced in SWOG-0014 ³, for example, has suggested the use of R-CHOP (rituximab + CHOP) with or without radiation therapy but only on the basis of historical comparison to prior studies.[6][Level of evidence: 3iiiDiii] A preliminary study using CHOP with or without etoposide for patients older than 60 years suggested improvement in EFS and OS for treatment delivered every 2 weeks versus the standard 3-week regimen.[7]

A randomized study (RICOVER-60 ⁴) of 1,222 patients older than 60 years compared R-CHOP given every 2 weeks for six or eight cycles to CHOP given every 2 weeks for six or eight cycles.[8] With a median follow-up of 35 months, the EFS favored R-CHOP given every 2 weeks for six or eight cycles (EFS, RR = 0.5 [0.40–0.65], P < .001). The OS favored R-CHOP for only six cycles because of increased toxicity in the eight-cycle arm (RR of death = 0.63 [0.46–0.85], P = .003).[8][Level of evidence: 1iiA] There was no comparison to standard R-CHOP or CHOP given every 3 weeks.

Standard treatment options:

• Chemotherapy with or without IF-XRT
  • R-CHOP (four to eight cycles).
  • R-CHOP (three to eight cycles) plus IF-XRT.

There are no comparative studies to establish an optimal number of chemotherapy cycles for patients with early stage disease.

Treatment options under clinical evaluation:

• R-ACVBP (rituximab + doxorubicin + cyclophosphamide + vindesine + bleomycin + prednisone).[5].

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with aggressive, stage I adult non-Hodgkin lymphoma ⁵ and aggressive, contiguous stage II adult non-Hodgkin lymphoma ⁶. 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 ⁷.

References

1. Bonnet C, Fillet G, Mounier N, et al.: CHOP alone compared with CHOP plus radiotherapy for localized aggressive lymphoma in elderly patients: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol 25 (7): 787-92, 2007.  [PUBMED Abstract]
   
   
2. Miller TP, Dahlberg S, Cassady JR, et al.: Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. N Engl J Med 339 (1): 21-6, 1998.  [PUBMED Abstract]
   
   
3. Miller TP, Leblanc M, Spier C, et al.: CHOP alone compared to CHOP plus radiotherapy for early stage aggressive non-Hodgkin's lymphomas: update of the Southwest Oncology Group (SWOG) randomized trial. [Abstract] Blood 98 (11): A-3024, 2001. 
   
   
4. Horning SJ, Weller E, Kim K, et al.: Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin's lymphoma: Eastern Cooperative Oncology Group study 1484. J Clin Oncol 22 (15): 3032-8, 2004.  [PUBMED Abstract]
   
   
5. Reyes F, Lepage E, Ganem G, et al.: ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma. N Engl J Med 352 (12): 1197-205, 2005.  [PUBMED Abstract]
   
   
6. Persky DO, Unger JM, Spier CM, et al.: Phase II study of rituximab plus three cycles of CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell lymphoma: Southwest Oncology Group study 0014. J Clin Oncol 26 (14): 2258-63, 2008.  [PUBMED Abstract]
   
   
7. Pfreundschuh M, Trümper L, Kloess M, et al.: Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood 104 (3): 634-41, 2004.  [PUBMED Abstract]
   
   
8. Pfreundschuh M, Schubert J, Ziepert M, et al.: Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol 9 (2): 105-16, 2008.  [PUBMED Abstract]
   
   

Glossary Terms

Randomized, controlled, nonblinded clinical trial with total mortality as an endpoint. See Levels of Evidence for Adult and Pediatric Cancer Treatment Studies (PDQ®) for more information.

Nonconsecutive case series with progression-free survival as an endpoint. See Levels of Evidence for Adult and Pediatric Cancer Treatment Studies (PDQ®) for more information.