Chemotherapy for acute myelogenous leukemia in the elderly with cytarabine, mitoxantrone, and granulocyte-macrophage colony-stimulating factor

Remission induction chemotherapy for acute myelogenous leukemia typically c ombines cytarabine with an anthracycline or anthracycline derivative. To da te, no specific combination has emerged as more efficacious than any other. To reduce toxicity and shorten the duration of neutropenia. hematopoietic growth factors are often added to the chemotherapy regimen, especially in e lderly patients. In all prospective, randomized, growth factor trials to da te, daunorubicin has been the drug selected for combination with cytarabine . We hypothesized that mitoxantrone might be as efficacious in this patient population with perhaps less toxicity when combined with granulocyte-macro phage colony-stimulating factor (GM-CSF). Patients older than age 55 years with a diagnosis of either de novo or secondary. untreated acute myelogenou s leukemia were eligible for this clinical trial. Eligible patients were tr eated with cytarabine 100 mg/m(2) infused as a continuous infusion daily fo r 7 days and mitoxantrone 12 mg/m(2) bolus intravenously for the first 3 da ys of cytarabine. A second cycle of chemotherapy was administered on the fo urteenth day of treatment if marrow aplasia was not achieved with the first cycle. Once aplasia was achieved. GM-CSF 250 mug/m(2) was given subcutaneo usly daily until neutrophil recovery. Those patients who achieved complete remission were treated with two cycles of intermediate-dose cytarabine (400 mg/m(2) daily for 5 days) and with GMCSF as consolidation therapy. Of the 30 patients treated, the median age was 69 years (range: 55-76 years) and 1 8 patients were older than 65 years of age. Seven (23%) patients had second ary acute leukemia and 12 (40%) had poor-risk cytogenetics. Nineteen (63%) achieved a complete remission. Eleven patients were either refractory to tr eatment or died during their treatment. The toxicity encountered was no mor e than that reported in similar studies using daunorubicin in combination w ith cytarabine. Long-term survival was poor, with a median disease-free sur vival of only 8.1 months in patients who achieved complete remission. In th is elderly population of patients with high-risk acute myelogenous leukemia , this combination of cytarabine, mitoxantrone. and GM-CSF resulted in an a dequate remission rate with acceptable toxicity. Long-term survival, howeve r, was poor and innovative treatment approaches to maintain remission are n eeded.