MACOP-B VS F-MACHOP REGIMEN IN THE TREATMENT OF HIGH-GRADE NON-HODGKINS-LYMPHOMAS

A prospective randomized study on aggressive non-Hodgkin's lymphomas w as conducted by investigators at several Italian institutions with the intent of comparing two third-generation conceptually different regim ens: the regimen containing methotrexate with leucovorin rescue, doxor ubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACO P-B), a short-term continuous twelve-week therapy, and F-MACHOP (5-flu orouracil, methotrexate with leucovorin rescue, cytarabine, cyclophosp hamide, doxorubicin, vincristine, and prednisone), a monthly intensive cyclic treatment combining prednisone with six active non-cross-resis tant cytotoxic drugs. The goals of this study were the response rate, relapse-free survival, and incidence of hematologic and nonhematologic toxicities. Two hundred-eighty-six patients included between 15 and 6 0 years fulfilled the criteria for entry to the study; 140 patients we re treated with MACOP-B and 146 with F-MACHOP. The minimum follow-up w as 24 months. Clinical characteristics of all patients were similar an d known prognostic factors were equally distributed between the two gr oups. Complete remission (CR) was achieved by 61% and 67% of the patie nts treated with MACOP-B and F-MACHOP, respectively; 4% and 6% were pr imarily resistant, 2% and 5%, respectively, died of causes directly re lated to therapy. At 50 months, 74% of all CR patients were alive with out disease and there were no significant differences in relapse-free survival between the two groups: 75% in the F-MACHOP group and 73% in the MACOP-B group at 50 months. There was a higher incidence of mucosi tis among patients treated with MACOP-B than among those given F-MACHO P (11% vs 3.5%). Higher incidences of severe cytopenia (51% vs 21%) an d of fatal sepsis (5% vs 2%) were recorded among patients treated with F-MACHOP than with MACOP-B. The third-generation regimens, F-MACHOP a nd MACOP-B, are as effective as other regimens. A prognostic analysis taking into account the principal covariates (age, symptoms, stage, se rum lactate dehydrogenase, mediastinum involvement, bulky disease, his tology, therapy, and dose intensity) was assessed for their impact on complete response rate incidence and on relapse rate from complete res ponse by multivariate analysis. The linear logistic model showed that symptoms, advanced stage, mediastinum involvement, and bulky disease a re prognostic factors that increase the risk of a lower rate of comple te response. These data confirm the important role of a pretreatment s election for the poor-risk patients and, on the basis of these paramet ers, it will probably be possible to consider these patients for high- dose therapy with autologous bone marrow transplantation or autologous hematopoietic stem-cell support.