Sequential Standard-Dose Cytosine Arabinoside/Mitoxantrone Therapy (SAM) in Adults with Acute Myeloid Leukemia

During the last 2 decades different treatment strategies have been tested as remission induction therapy in acute myeloid leukemia (AML) in adults in several large trials. The present standard regimen includes cytosine arabinoside (200 mg/m2 per day) for 7 days and an anthracycline derivate like daunorubicin (60 mg/m’ per day) for 3 days [1]. The double-induction strategy with repetition of two identical chemotherapy courses prolongs disease-free survival [2]. Recently the new anthraquinone derivate mitoxantrone has been introduced in the therapy of refractory and relapsed AML. In combination with high-dose cytosine arabinoside or etoposide, a high efficacy of the drug could be demonstrated [3, 4]. However, experience using mitoxantrone in primary therapy of AML is still limited. In randomized trials Phillips et al. [5] and Arlin et al. [6] demonstrated a marginal, not significant superiority of mitoxantrone compared to daunorubicin. In 1980 Burke et al. [7] reported the results of a sequential chemotherapy modality timed to coincide with enhanced tumor proliferation after initial aplasia induction. On this basis, Capizzi et al. [8] and Hiddemann et al. [9] applied high-dose cytosine arabinoside in a sequential mode and showed an enhanced efficacy compared to conventional chemotherapy. In a prospective multicenter trial we are currently evaluating the efficacy and toxicity of a double-induction therapy with standard-dose cytosine arabinoside and mitoxantrone in a sequential mode (SAM protocol) in adults with untreated AML.