A randomized comparison of methotrexate dose and the addition of bleomycin to chop therapy for diffuse large cell lymphoma and other non-Hodgkin's lymphomas cancer and leukemia group B study 7851

Abstract

In 1978, Cancer and Leukemia Group B initiated a randomized study to determine the usefulness of the addition of bleomycin and/or high-dose methotrexate to standard therapy for the treatment of certain adult non-Hodgkin's lymphomas. Between 1978 and 1985, 177 patients with diffuse large cell lymphoma (DLCL) and 97 patients with other intermediate-grade non-Hodgkin's lymphoma were randomized to receive therapy with three courses of cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) every 3 weeks with or without low-dose bleomycin by continuous IV infusion. Responders after three courses were further randomized to 3 weeks of therapy with either high-dose methotrexate (3 gm/m2/week intravenously with leucovorin rescue) or standard-dose methotrexate (30 mg/m2/week orally without rescue). Therapy was concluded with three additional courses of CHOP. Neither the addition of low-dose infusion bleomycin nor the use of high-dose rather than low-dose methotrexate had significant effects on response for patients with DLCL; complete response rates for the four treatment programs ranged from 47% to 51%. Median failure-free survival (FFS) for the entire group of DLCL patients was 12 months; 5-year FFS was 27%. There was no significant effect on FFS from the addition of either low-dose bleomycin to CHOP (5-year FFS: CHOP, 28%; CHOP-B, 26%, P = 0.81), or from the use of different doses of methotrexate (5-year FFS: high-dose, 34%; standard-dose, 33%, P = 0.51). Patients with follicular large cell lymphoma, with or without diffuse areas, had a better FFS (5-year FFS, 47%) than patients with DLCL (5-year FFS, 27%), while the patients with the other histopathologic subtypes of diffuse lymphomas had the poorest FFS (5-year FFS, 16%).

Prospective analysis of treatment outcome and prognostic factors in patients with T‐cell lymphomas treated by CEOP‐B: single institutional study

“…Therefore, further trials to minimise and overcome severe neutropenia using our protocol are needed. Despite of the relatively low incidence of CR in our study, the 5-year OS of the patients enrolled (49%) was similar to prior reports on T-cell NHL (Case, 1983;Sampi et al, 1983;Gottlieb et al, 1990). Differences in study design as well as patient characteristics, such as comparatively young median age (47 years) and good PS (PS 0-1, 64%), may explain these findings.…”

“…The CEOP-B combination chemotherapy comprises myelosuppressive (cyclophosphamide, epirubicine) and non-myelosuppressive (vincristine and bleomycin) drugs with a proven effectiveness in patients with NHL (Case, 1983;Sampi et al, 1983;Gottlieb et al, 1990). The potential antitumour synergy of these drugs with non-overlapping toxicity profiles, as well as the absence of cross-resistance, makes this combination an attractive frontline regimen for the treatment of patients with NHL.…”

Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma

“…As the complete remission rates were similar in the 2 treatment groups, the advantage in the ACVBP appeared to be related to a longer disease-free survival, with an 18% difference at 5 years. Several randomized studies have compared CHOP with modified CHOPlike regimens [24][25][26] or other chemotherapy combinations as m-BACOD, MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, bleomycin, prednisone), or PROMACECytaBOM (prednisone, doxorubicin, cyclophosphamide, etoposide, cytarabine, bleomycin, vincristine). 7,8,[27][28][29][30] With the exception of the study from the Australian and New Zealand Lymphoma Group, 30 all of the studies failed to show any advantage of the new regimen.…”

The Cancer and Leukemia Group B Lymphoma Committee

“…Numerous attempts were made to improve on the efficacy of this combination by adding other agents that were presumed to be non -cross-resistant and with nonoverlapping toxicities (18)(19)(20). The CALGB developed one such regimen in which the dose of methotrexate and the role of bleomycin were evaluated in the context of the other agents in CHOP (21). In CALGB 7851, 177 patients with diffuse large B-cell lymphoma and 97 with other aggressive histologies received three cycles of CHOP every 3 weeks with or without bleomycin.…”