Superiority of second over first generation chemotherapy in a randomized trial for stage III-IV intermediate and high-grade Non-Hodgkin's Lymphoma (NHL): The 1980–1985 EORTC trial

Abstract

A first-generation CHOP-like cyclic combination chemotherapy (CT) regimen using cyclophosphamide 600 mg/m2 IV d1, hydroxorubicin (doxorubicin) 50 mg/m2 IV d1, VM26 60 mg/m2 IV d1, and prednisone 40 mg/m2 PO d1-5 (CHVmP) was compared to a second-generation combination wherein vincristine 1.4 mg/m2 IV and bleomycin 6 mg/m2 IM/IV were added at mid-interval (d15) to the former drugs (CHVmP + VB) in the treatment of intermediate- and high-grade malignant NHL. From April 1980 to January 1986, 141 eligible patients with stage III-IV unfavorable histologies (except T lymphoblastic NHL) entered this EORTC randomized trial. In both arms adjuvant radiotherapy (30 Gy) was given in instances of bulky or residual disease. In all patient subsets the outcome favored the second-generation regimen. The difference was even greater in patients with Diffuse Large Cell Lymphoma (DLCL). At 5 years, overall survival was 53% with CHVmP + VB versus 29% (p = 0.002). The advantage was due to a higher complete remission (CR) rate (80% versus 50%, p = 0.01). Indeed, once CR was achieved the relapse-free survival (RFS) was not significantly influenced (59% versus 49%). No significant additional toxicity could be attributed to vincristine and bleomycin. This study demonstrates a clear benefit for intermediate- and high-risk malignant NHL and particularly DLCL from intercalating non-myelotoxic drugs at mid-cycle intervals, without adverse effects.

Long-term risk of cardiovascular disease after treatment for aggressive non-Hodgkin lymphoma

“…[32][33][34][35] No cumulative total dose doxorubicincomplication relation could be estimated, because dose information of salvage treatment was often lacking.…”

ESHAP Salvage Therapy for Refractory and Relapsed Non-Hodgkin's Lymphoma: A Single Center Experience

“…The previous conventional chemotherapy regimens have attained complete remission in about 50% of patients1-3). The best available regimen, the CHOP combination chemotherapy, has been widely used, but the prognosis of the partial responders to CHOP therapy is very poor with only 0~25% of patients becoming long-term survivors17).…”

“…The treatment of non-Hodgkin's lymphoma (NHL) has been considerably improved for attaining complete remission and long-term survival in approximately 50% of patients1-3). However, the prognosis of the patients who are refractory to treatment or who relapse with NHLs is dismal at best4, 5).…”

MACOP-B Regimen in Non-Hodgkin's Lymphoma

“…However, a dose-intensive third generation regimen Pro-MACE-CytaBOM has recently in a randomized study been shown to improve survival when compared with a second generation regimen ProMACE-MOPP ( lo), and another randomized study showed that the addition of bleomycin and vincristine at mid-interval (d. 15) of a CHOP-like first generation regimen CHVmP (cyclophosphamide, doxorubicin, VM-26, and prednisone) resulted in a better outcome (11). A feasible and well-tolerated way to combine active drugs with low myelotoxicity, such as bleomycin, vincristine and methotrexate, with more myelotoxic drugs may be an important reason for these results.…”