A Randomized Study of MP versus Alternating VAD-VND(N=Mitoxantrone)/MP as Primary Therapy for Multiple Myeloma

Abstract

Although in the last years new insights have been gained into the biology of multiple myeloma (MM), therapeutic progress has been modest since the introduction of alkylating agents (usually melphalan and cyclophosphamide) nearly three decades ago. With few exceptions, a large number of clinical trials exploring the use of alternating or sequential drug combinations have failed to show any survival advantage over the standard association of melphalan and steroids (MP), which remains the cornerstone of treatment of MM in community practice. More recently, important advances in the management of MM have included the recognition that i) the use of high-dose glucocorticoids, eventually combined with 4-day continuous infusions of vincristine and doxorubicin (VAD regimen), is highly effective, even in alkylating agent-resistant/relapsed MM, and ii) recombinant α-2b interferon (IFN), may be a useful tool either as part of the induction treatment or as maintenance therapy for responsive patients with stable disease. On the basis of these observations, and in an attempt to improve the response rate and survival in newly diagnosed patients with an unfavourable prognosis, a prospective randomized clinical trial comparing MP with alternating VAD/MP, with alternating VND(N=mitoxantrone)/MP, with subsequent IFN as maintenance therapy for responsive patients, was started in Italy in November 1990.