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]
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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).[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,  but a re-evaluation for OS at 9 years showed no difference in either arm of the study.[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).[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).[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.[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.
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. 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).[Level of evidence: 1iiA] There has been no comparison to standard R-CHOP or CHOP given every 3 weeks.