Liposomal daunorubicin plus cytosine arabinoside for elderly patients with acute myeloid leukemia: The gimema experience

The frequent overexpression of the multidrug resistance gene (MDR) product, the P-glycoprotein (P-gp), may contribute to the higher rate of treatment failure in elderly AML patients. Liposomal daunorubicin is characterized by a higher tumor cell delivery with improved pharmacokinetic and therapeutic indices, resulting in a reduced toxicity profile. Since November 1998 eleven GIMEMA centers treated 51 elderly (>60 years) AML patients at diagnosis (excluding M3) with two courses of DaunoXome (NeXstar Pharm. Italy), at the dosage of 80 mg/m2 for 3 consecutive days in combination with cytosine arabinoside (Ara-C) at the dosage of 100 mg/m2 for 7 consecutive days. Median age was 69 years (range 61–78) and the median WBC values were 13.0 × 109/L (range 1–450). Twenty-eight patients (55%) achieved CR after either first (25 cases) or second (3 cases) cycles. Induction deaths due to toxicities were 5 (10%), due to multiorgan failure (1), infection (4). A prolonged hypoplasia (>40 days) occurred in 1 case, while 17 patients (35%) were resistant. Non-hematological toxicities >2 WHO occurred in 13 patients, consisting mainly of expected side effects (mucosytis, diarrhoea, FUO): only 2 patients showed cardiovascular toxicity. Peripheral recovery occurred at a median of 22 days for PMN >0.5 × 109/L, and 21 days for Plts >20 × 109/L. To now, 18 patients are in continuous CR after a median of 5 months, 9 relapsed after a median of 3.5 months and 1 died in CR. A DNX-based therapy seems to be a feasible approach in elderly AML and further prospective studies with increased doses will be planned.