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Late phase II study of amrubicin in previously untreated patients with non-Hodgkin's lymphoma (NHL).
Background: We evaluated the efficacy and safety of amrubicin, a third generation synthetic anthracycline, in combination with cyclophosphamide, vincristine and prednisolone (ACOP) in patients with previously untreated aggressive non-Hodgkin's lymphoma (NHL). Methods: Previously untreated patients with intermediate or high grade NHL were treated with 8 cycles of amrubicin, 100 mg/m2, cyclophosphamide, 750 mg/m2, and vincristine, 1.4 mg/m2 (maximum 2.0 mg), on day 1, and prednisolone, 60 mg/m2/day day 1-5 every 21 days. Patients were evaluated for response and left ventricular ejection fraction (LVEF) every 2 cycles, and electrocardiogram at every cycle. The primary endpoint was response rate; secondary endpoints were survival, cardiac safety, and general safety. Results: Fifty-six patients were eligible and received a median of 8 treatment cycles. The median follow- up period was 57.1 months. Most patients had diffuse large B-cell lymphoma (76.8%). The response rate was 92.9%; the complete response (CR) and CRu rate was 69.6%. The 2- and 5-years survival rates were 76.2% and 58.7%, respectively. Reversible myelosuppression was the most common adverse event. Grade 3/4 neutropenia, anemia, thrombocytopenia and febrile neutropenia were reported in 82.5%, 19.3%, 8.8% and 7% of patients, respectively. There were no treatment-related deaths or patients experiencing cardiomyopathy. LVEF did not change during the course of treatment. Conclusions: The response rate and survival in non-Hodgkin's lymphoma patients treated with ACOP were comparable to those achieved with CHOP in other studies, but ACOP had virtually no reduction of LVEF up to a cumulative amrubicin dose of 800 mg/m2. This suggests that amrubicin has little chronic cardiotoxicity. ACOP should be evaluated in combination with rituximab (R) and then compared to R-CHOP.