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:

• ACVBP: doxorubicin + cyclophosphamide + vindesine + bleomycin + prednisone.
• CHOP: cyclophosphamide + doxorubicin + vincristine + prednisone.
• CNOP: cyclophosphamide + mitoxantrone + vincristine + prednisone.
• m-BACOD: methotrexate + bleomycin + doxorubicin + cyclophosphamide + vincristine + dexamethasone + leucovorin.
• MACOP-B: methotrexate + doxorubicin + cyclophosphamide + vincristine + prednisone fixed dose + bleomycin + leucovorin.
• ProMACE CytaBOM: prednisone + doxorubicin + cyclophosphamide + etoposide + cytarabine + bleomycin + vincristine + methotrexate + leucovorin.
• R-CHOP: Rituximab, an anti-CD20 monoclonal antibody, + cyclophosphamide + doxorubicin + vincristine + prednisone.

The treatment of choice for patients with advanced stages of aggressive non-Hodgkin lymphoma (NHL) is combination chemotherapy, either alone or supplemented by local-field radiation therapy.[1]

Doxorubicin-based combination chemotherapy produces long-term disease-free survival in 35% to 45% of patients.[2,3,4] Higher cure rates have been reported in single-institution studies than in cooperative group trials.

A prospective randomized trial of four regimens (CHOP, ProMACE CytaBOM, m-BACOD, and MACOP-B) for patients with diffuse large B-cell lymphoma showed no difference in overall survival (OS) or time-to-treatment failure (TTF) at 3 years.[4][Level of evidence: 1iiA] Other randomized trials have confirmed no advantage among the standard doxorubicin-based combinations versus CHOP.[5,6][Level of evidence: 1iiA] A randomized clinical trial failed to demonstrate a beneficial effect of adjuvant radiation therapy in advanced-stage aggressive NHL.[7]

The combination of rituximab and CHOP (R-CHOP) showed improvement in event-free survival (EFS) and OS compared with CHOP alone in 399 advanced-stage patients with diffuse large B-cell lymphoma older than 60 years (EFS = 57% vs. 38%, P = .002, and OS = 70% vs. 57%, P = .007 at 2 years).[8][Level of evidence: 1iiA] At 5-years' median follow-up, the OS of patients who received R-CHOP compared with patients who received CHOP was 58% vs. 45%, P < .007.[9] Similarly, for 326 evaluable patients younger than 61 years, R-CHOP showed improvement in EFS and OS compared to CHOP alone (EFS = 79% vs. 59%, P = .001, and OS = 93% vs. 84%, P = .001 at 3 years).[10][Level of evidence: 1iiA] These two studies established R-CHOP as the standard regimen for newly diagnosed patients with diffuse large B-cell lymphoma.[11]

A trial of 635 patients, aged 61 to 69 years, with stage III and stage IV disease, elevated lactate dehydrogenase (LDH), or performance status of 2 to 4, randomized patients to receive CHOP or ACVBP. With a median follow-up of 68 months, patients who received ACVBP had superior EFS and OS (EFS = 39% vs. 29% at 5 years, P = .005 and OS = 46% vs. 38% at 5 years, P = .036).[12][Level of evidence: 1iiA] Two prospective randomized trials that compared CHOP with CNOP for patients aged 60 years and older with diffuse large cell lymphoma showed a significant advantage for CHOP in terms of disease-free survival and OS.[13,14][Level of evidence: 1iiA] Two other randomized trials of patients aged 70 years and older confirm the superiority of CHOP over other less toxic regimens in progression-free survival and OS.[15,16][Level of evidence: 1iiA] Although infusion regimens have been proposed, a randomized trial of infusional CHOP versus standard CHOP therapy showed no improvement in relapse-free survival or OS.[17][Level of evidence: 1iiA] Clinical trials such as SWOG-9349, for example, continue to explore modifications of CHOP and rituximab with CHOP by increasing doses, reducing intervals between cycles, and combining new drugs with new mechanisms of action.[12,18,19,20]