COMPARISON OF MELPHALAN AND PREDNISONE WITH VINCRISTINE, CARMUSTINE, MELPHALAN, CYCLOPHOSPHAMIDE, AND PREDNISONE IN THE TREATMENT OF MULTIPLE-MYELOMA - RESULTS OF EASTERN-COOPERATIVE-ONCOLOGY-GROUP STUDY E2479

BACKGROUND. The Eastern Cooperative Oncology Group (ECOG) performed a Phase III comparison of melphalan and prednisone (MP) with vincristine , carmustine (BCNU), melphalan, cyclophosphamide, and prednisone (VBMC P) in an attempt to determine which of these regimens should be the st andard treatment for multiple myeloma. METHODS. Four hundred seventy-n ine previously untreated patients with multiple myeloma from 23 ECOG i nstitutions were enrolled. Treatment, assigned by randomization, consi sted of either 4-week cycles of MP or 5-week cycles of VBCMP. After 1 year of induction therapy, patients received MP or VBMCP maintenance t herapy at 6- and 8-week intervals, respectively, until relapse. Patien ts who experienced treatment failure with MP were eligible for crossov er therapy with VBMCP. RESULTS. Objective responses were obtained for 51% of patients receiving MP, as compared with 72% of patients receivi ng VBMCP (P < 0.001). Response duration was also longer with VBMCP (me dian, 18 months with MP vs. 24 months with VBMCP; P = 0.007). Overall survival was not significantly different between MP and VBMCP (P = 0.3 0). The 5-year survival for VBMCP was 26%, as compared with 19% for MP . VBMCP was associated with more nausea, peripheral nerve toxicity, al opecia, and neutropenia, but the infection rate was equal to that obse rved with MP. Both regimens were generally well tolerated. The main ex ception was that elderly patients who were confined to bed had a highe r risk of death with VBMCP. The two regimens produced a similar incide nce of late secondary myelodysplastic syndrome and acute leukemia. Cro ssover VBMCP for patients failing with MP was only minimally effective , with an objective response rate of 20% and median survival of 11 mon ths after crossover. CONCLUSIONS. VBMCP is more effective than MP in p roducing and sustaining remission of multiple myeloma. It is associate d with a marginal survival advantage and an apparently greater chance of surviving 5 years for patients who can tolerate moderately intensiv e combination chemotherapy. (C) 1997 American Cancer Society.