Fludarabine and arabinosylcytosine therapy of refractory and relapsed acute myelogenous leukemia.
There is a strong association between ability of leukemia blasts to accumulate ara-CTP, the active metabolite of ara-C, and response to ara-C in patients with relapsed or refractory AML. Ara-C dose rates in excess of 0.5 g/m2/h do not produce further ara-CTP formation. In contrast, when given 4 h prior to ara-C at this dose rate, fludarabine, at doses that are free of neurotoxicity in CLL, enhances ara-CTP accumulation. This led us to administer fludarabine and ara-C to 59 patients with AML in relapse or unresponsive to initial therapy. Fludarabine was given at 30 mg/m2 once daily for 5 doses and ara-C at 0.5 g/m2/h for 2-6 h daily for 6 doses. Doses of fludarabine preceded those of ara-C by 4 h. Results with fludarabine and ara-C (FA) were compared with those of patients treated at M.D. Anderson with high-dose ara-C (HDAC) or intermediate-dose ara-C (IDAC). The complete remission rate with FA was 21/59 (36%) and the actuarial median CR duration 39 weeks. FA produced significantly higher remission rates than HDAC or IDAC in patients with initial remissions > 1 yr (14/20 vs 9/23 vs 6/18, p < 0.05). Response rates were similar for all three treatments in patients with initial remissions < 1 yr or with primary refractory disease. The regimen was well tolerated; one patient developed peripheral neuropathy. This low level of toxicity encourages combination with other antileukemia agents.
Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
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E
Estey
W
W
Plunkett
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V
Gandhi
M B
MB
Rios
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Kantarjian
M J
MJ
Keating
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001855:Bone Marrow Diseases / Q000139:chemically induced; D016026:Bone Marrow Transplantation; D003092:Colitis / Q000139:chemically induced; D003131:Combined Modality Therapy; D003231:Conjunctivitis / Q000139:chemically induced; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000139:chemically induced; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D012074:Remission Induction; D016879:Salvage Therapy; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
D003561:Cytarabine; D014740:Vidarabine; C024352:fludarabine