Treatment of multiple myeloma: A randomized study of three different regimens

The results of an Italian multicentric trial for treatment of symptomatic Multiple Myeloma (MM) are reported. One hundred and thirty-three previously untreated patients were singled out at random for three different chemotherapy schedules: Melphalan plus Prednisone (M.P.) x 6 monthly cycles; Vincristine plus Melphalan plus Cyclophosphamide plus Prednisone (VMCP) x 6 monthly cycles; Peptichemio, Cyclophosphamide, BCNU. Drugs in this latter schedule were administered sequentially, for a period of six months. Criteria for response, progression and relapse were those of the Southwestern Oncology Group. Fifteen patients in MP chemotherapy (35%) and 20 patients in VCMP chemotherapy (46%) achieved an objective response (decrease of at least 50% in the synthesis index of Monoclonal Component (M.C.)), While only 3 out of the other 21 patients assigned to the third schedule responded to treatment. No significant differences were noted in the survival curves in either of the three treatment groups. The 38 responding patients did not receive maintenance therapy; no significant difference was found in remission duration between patients in MP and VCMP arms, with a median duration of 16 months for the whole group. No statistical difference was observed between survival and remission curves of patients with a 'response' (M. spike reduction > 75%) and those with 'improvement' (M. spike reduction between 75 and 50%). The authors conclude that the inclusion of Vincristine in a combination chemotherapy does not produce clear survival benefits; a longer induction period (12 cycles) could allow a better differentiation between MP and VMCP regimens

Treatment of multiple myeloma: A randomized study of three different regimens

The results of an Italian multicentric trial for treatment of symptomatic Multiple Myeloma (MM) are reported. One hundred and thirty-three previously untreated patients were singled out at random for three different chemotherapy schedules: Melphalan plus Prednisone (M.P.) x 6 monthly cycles; Vincristine plus Melphalan plus Cyclophosphamide plus Prednisone (VMCP) x 6 monthly cycles; Peptichemio, Cyclophosphamide, BCNU. Drugs in this latter schedule were administered sequentially, for a period of six months. Criteria for response, progression and relapse were those of the Southwestern Oncology Group. Fifteen patients in MP chemotherapy (35%) and 20 patients in VCMP chemotherapy (46%) achieved an objective response (decrease of at least 50% in the synthesis index of Monoclonal Component (M.C.)), While only 3 out of the other 21 patients assigned to the third schedule responded to treatment. No significant differences were noted in the survival curves in either of the three treatment groups. The 38 responding patients did not receive maintenance therapy; no significant difference was found in remission duration between patients in MP and VCMP arms, with a median duration of 16 months for the whole group. No statistical difference was observed between survival and remission curves of patients with a 'response' (M. spike reduction > 75%) and those with 'improvement' (M. spike reduction between 75 and 50%). The authors conclude that the inclusion of Vincristine in a combination chemotherapy does not produce clear survival benefits; a longer induction period (12 cycles) could allow a better differentiation between MP and VMCP regimens

MACOP-B vs F-MACHOP regimen in the treatment of high-grade non-Hodgkin's lymphomas

A prospective randomized study on aggressive non-Hodgkin's lymphomas was conducted by investigators at several Italian institutions with the intent of comparing two third-generation conceptually different regimens: the regimen containing methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B), a short-term continuous twelve-week therapy, and F-MACHOP (5-fluorouracil, methotrexate with leucovorin rescue, cytarabine, cyclophosphamide, doxorubicin, vincristine, and prednisone), a monthly intensive cyclic treatment combining prednisone with six active non-cross-resistant 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 60 years fulfilled the criteria for entry to the study; 140 patients were treated with MACOP-B and 146 with F-MACHOP. The minimum follow-up was 24 months. Clinical characteristics of all patients were similar and known prognostic factors were equally distributed between the two groups. Complete remission (CR) was achieved by 61% and 67% of the patients treated with MACOP-B and F-MACHOP, respectively; 4% and 6% were primarily resistant, 2% and 5%, respectively, died of causes directly related to therapy. At 50 months, 74% of all CR patients were alive without 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 mucositis among patients treated with MACOP-B than among those given F-MACHOP (11% vs 3.5%). Higher incidences of severe cytopenia (51% vs 21%) and of fatal sepsis (5% vs 2%) were recorded among patients treated with F-MACHOP than with MACOP-B. The third-generation regimens, F-MACHOP and MACOP-B, are as effective as other regimens. A prognostic analysis taking into account the principal covariates (age, symptoms, stage, serum lactate dehydrogenase, mediastinum involvement, bulky disease, histology, therapy, and dose intensity) was assessed for their impact on complete response rate incidence and on relapse rate from complete response by multivariate analysis. The linear logistic model showed that symptoms, advanced stage, mediastinum involvement, and bulky disease are prognostic factors that increase the risk of a lower rate of complete response. These data confirm the important role of a pretreatment selection for the poor-risk patients and, on the basis of these parameters, it will probably be possible to consider these patients for high-dose therapy with autologous bone marrow transplantation or autologous hematopoietic stem-cell support

Multiple myeloma: VMCP/VBAP alternating combination chemotherapy is not superior to melphalan and prednisone even in high-risk patients

The efficacy of alternating vincristine, melphalan (M), cyclophosphamide, prednisone/vincristine, carmustine, doxorubicin, and prednisone (VMCP/VBAP) polychemotherapy was compared with the M and prednisone (MP) regimen as induction treatment in multiple myeloma (MM). Three hundred four MM patients entered this study between March 1983 and July 1986; the analysis was performed in December 1989. The treatment groups did not show significant differences with respect to major prognostic factors. Median overall survival was 33.8 months. In the VMCP/VBAP and MP arms, after 12 induction chemotherapy cycles, 59.0% and 47.3% (P < .068) of the patients achieved an M component reduction greater than 50%. No significant difference was observed in the two treatment arms in terms of remission duration (21.3 v 19.6 months, P < .66) and survival (31.6 v 37.0 months, P < .28). Patients younger than 65 years did not show any advantage from the alternating polychemotherapy. At diagnosis, the plasma cell labeling index (LI) and serum beta-2 microglobulin (β2-m) were evaluated in 173 and 183 patients, respectively. A significantly reduced survival was observed for patients with LI ≥ 2% (16.4 months) or β2-m ≥ 6 mg/L (20.4 months). Even in these poor-risk subgroups, VMCP/VBAP was not superior to M

Multiple myeloma: VMCP/VBAP alternating combination chemotherapy is not superior to melphalan and prednisone even in high-risk patients

The efficacy of alternating vincristine, melphalan (M), cyclophosphamide, prednisone/vincristine, carmustine, doxorubicin, and prednisone (VMCP/VBAP) polychemotherapy was compared with the M and prednisone (MP) regimen as induction treatment in multiple myeloma (MM). Three hundred four MM patients entered this study between March 1983 and July 1986; the analysis was performed in December 1989. The treatment groups did not show significant differences with respect to major prognostic factors. Median overall survival was 33.8 months. In the VMCP/VBAP and MP arms, after 12 induction chemotherapy cycles, 59.0% and 47.3% (P < .068) of the patients achieved an M component reduction greater than 50%. No significant difference was observed in the two treatment arms in terms of remission duration (21.3 v 19.6 months, P < .66) and survival (31.6 v 37.0 months, P < .28). Patients younger than 65 years did not show any advantage from the alternating polychemotherapy. At diagnosis, the plasma cell labeling index (LI) and serum beta-2 microglobulin (β2-m) were evaluated in 173 and 183 patients, respectively. A significantly reduced survival was observed for patients with LI ≥ 2% (16.4 months) or β2-m ≥ 6 mg/L (20.4 months). Even in these poor-risk subgroups, VMCP/VBAP was not superior to M