Aggressive, Stage I and Contiguous Stage II Adult Non-Hodgkin Lymphoma

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.)

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).[1,2,3,4,5]

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 (EST-1484) 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-S0014, 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 (DSHNHL-1999-1A) 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, relative risk [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 has been 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]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with aggressive, stage I adult non-Hodgkin lymphoma and aggressive, contiguous stage II adult non-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. 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.
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.
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.
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.
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.
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.
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.