Combination of Mitoxantrone and Etoposide in the Treatment of Myelodysplastic Syndromes Transformed into Acute Myeloid Leukemia

Abstract

Mitoxantrone and etoposide have both been shown to be effective in de novo acute myeloid leukemia. Therefore, the combination of mitoxantrone and etoposide, the NOVE regimen, was examined in the treatment of myelodysplastic syndromes (MDS) transformed into acute myeloid leukemia (AML). Twenty-one previously untreated patients (eight females, thirteen males) with a median age of 56 years (range 28–67 years) were studied. Diagnosis of MDS was made within the range of six months to three years before transformation into AML occurred. The NOVE regimen consisted of mitoxantrone 10mg/m²day 1–5, and of etoposide 100 mg/m² day 1–5. After one single course of therapy eleven patients achieved a complete remission (CR) and three patients a partial remission (PR). Nine patients (six in CR and three in PR) received a second course, and the PR was completed to a CR in one patient. Thus, the overall response rate was 66% (14/21 patients), and the CR rate was 57% (12/21 patients). Median duration of CR was 7 months (range 2–10 months). Median survival was 10 months (range 3–20 months) for complete responders and 3 months (range 1–10 months) for patients who did not achieve a CR. For patients with subsequent CR, median time of granulocytopenia (<500/μl) and thrombocytopenia (<20.000/μl) was 20 days and 18 days, respectively. In conclusion, the NOVE regimen appears to be effective in AML secondary to MDS. However, strategies for remission maintenance are warranted.

Key Words:

• Mitoxantrone
• etoposide
• myelodysplastic syndromes
• secondary acute myeloid leukemia