Randomised controlled trials (RCTs) that compared high-dose intensity doxorubicin (more than 16.6mg/m2/week) in cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy with standard CHOP in patients with aggressive non-Hodgkin's lymphoma were eligible for inclusion. Eligible trials had to report sufficient data to allow the calculation of odds ratios or relative risks with 95% confidence intervals. Trials that administered any biological agent (rituximab, interferon) and/or consolidated with bone marrow transplantation were excluded, as were trials restricted to patients with low-grade lymphomas or localised disease.
The primary outcomes were five-year overall survival and event-free survival. Complete response rate was eligible as a secondary outcome. Outcome definitions were further defined in the review.
Trials included in the review were all phase III RCTs. Six different regimens were investigated overall survival: MACOP-B plus 25mg/m2/week doxorubicin; CHOP14 plus 25mg/m2/week doxorubicin; CHOEP14 plus 25mg/m2/week doxorubicin; I-CHOP plus35 mg/m2/week doxorubicin; PACEBOM plus 17.5mg/m2/week doxorubicin; and ACVP plus 25mg/m2/week doxorubicin. Dosing schedules and intervention details were defined in the review. CHOP regimens were given for six or eight (or from six to eight) cycles. Most trials included participants of all ages (actual ages ranged from 15 to 81 years). The number of patients in the trials with B-cell involvement ranged from 70 to 94.2%; from 59.8 to 87.4% of participants had diffuse large B-cell lymphoma; and 2.7 to 65.7% had a high/high-intermediate International Prognostic Index (where reported).
Studies were assessed for inclusion by two reviewers and reviewed by a third reviewer.