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 combines cytarabine with an anthracycline or anthracycline derivative. To date, 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 elderly patients. In all prospective, randomized, growth factor trials to date, 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-macrophage colony-stimulating factor (GM-CSF). Patients older than age 55 years with a diagnosis of either de novo or secondary, untreated acute myelogenous leukemia were eligible for this clinical trial. Eligible patients were treated with cytarabine 100 mg/m2 infused as a continuous infusion daily for 7 days and mitoxantrone 12 mg/m2 bolus intravenously for the first 3 days of cytarabine. A second cycle of chemotherapy was administered on the fourteenth day of treatment if marrow aplasia was not achieved with the first cycle. Once aplasia was achieved, GM-CSF 250 microg/m2 was given subcutaneously daily until neutrophil recovery. Those patients who achieved complete remission were treated with two cycles of intermediate-dose cytarabine (400 mg/m2 daily for 5 days) and with GM-CSF as consolidation therapy. Of the 30 patients treated, the median age was 69 years (range: 55-76 years) and 18 patients were older than 65 years of age. Seven (23%) patients had secondary acute leukemia and 12 (40%) had poor-risk cytogenetics. Nineteen (63%) achieved a complete remission. Eleven patients were either refractory to treatment or died during their treatment. The toxicity encountered was no more than that reported in similar studies using daunorubicin in combination with cytarabine. Long-term survival was poor, with a median disease-free survival of only 8.1 months in patients who achieved complete remission. In this elderly population of patients with high-risk acute myelogenous leukemia, this combination of cytarabine, mitoxantrone, and GM-CSF resulted in an adequate remission rate with acceptable toxicity. Long-term survival, however, was poor and innovative treatment approaches to maintain remission are needed.
Department of Hematology and Medical Oncology, Cleveland Clinic Foundation, Ohio 44195, USA. kalaycm@ccf.org
M
M
Kalaycio
B
B
Pohlman
P
P
Elson
A
A
Lichtin
M
M
Hussein
B
B
Tripp
S
S
Andresen
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009504:Neutrophils / Q000187:drug effects
D003561:Cytarabine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008942:Mitoxantrone