title: Idarubicin, cytarabine, and pravastatin as induction therapy for untreated acute myeloid leukemia and high-risk myelodysplastic syndrome.
abstract: Previous studies suggest that idarubicin/cytarabine(ara-C)/pravastatin (IAP) is an active salvage regimen for patients with AML. We therefore investigated this regimen in patients with newly-diagnosed AML or MDS (≥10% blasts). Patients were eligible if the anticipated treatment-related mortality (TRM) was <10%. Patients received pravastatin (1,280 mg/day po; days 1-8), cytarabine (1.5 g/m(2) /day; days 4-7), and idarubicin (12 mg/m(2) /day, days 4-6). Up to 3 cycles of consolidation with a shortened course was permitted. The primary endpoints were "good CR" rate (CR on day 35 without minimal residual disease) and TRM in the first 28 days. The study was to stop if after each cohort of 5 patients (a) the Bayesian posterior probability was < 5% that the true "good CR rate" was ≥ 70% or (b) the posterior probability was >25% that the TRM rate was ≥5%. Twenty-four patients were included. Conventional CR was achieved in 15 (63%) patients but only 12 (50%) achieved "good CR". 4 of 12 (33%) patients with "good CR" relapsed at median of 16 weeks (10.5-19). Five (21%) patients had refractory disease. Survival probability at 1 year was 72% (48.7-64). Two (8.3%) patients died within 28 days from multiorgan failure. The most common grade 3-4 adverse effects were febrile neutropenia (75%) and diarrhea (25%). Based on the stopping rules accrual ceased after entry of these 24 patients. IAP did not meet the predefined efficacy criteria for success. Therefore, we would not recommend this regimen for phase three testing in this patient subset.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.|Medical Oncology Division, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Mazyar
authors.initials: M
authors.lastname: Shadman
authors.affiliation: Swedish Cancer Institute, Swedish Medical Center, Seattle, Washington.
authors.forename: Raya
authors.initials: R
authors.lastname: Mawad
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Carol
authors.initials: C
authors.lastname: Dean
authors.affiliation: Department of Pharmacy, University of Washington, Seattle, Washington.
authors.forename: Tara L
authors.initials: TL
authors.lastname: Chen
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Shannon-Dorcy
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Vicky
authors.initials: V
authors.lastname: Sandhu
authors.affiliation: Hematology Division, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Hendrie
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.|Medical Oncology Division, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Bart L
authors.initials: BL
authors.lastname: Scott
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.|Hematology Division, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Rol B
authors.initials: RB
authors.lastname: Walter
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.|Hematology Division, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Becker
authors.affiliation: Swedish Cancer Institute, Swedish Medical Center, Seattle, Washington.
authors.forename: John M
authors.initials: JM
authors.lastname: Pagel
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.|Hematology Division, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Elihu H
authors.initials: EH
authors.lastname: Estey
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D060828:Induction Chemotherapy; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000401:mortality*; D017035:Pravastatin / Q000008:administration & dosage; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D003561:Cytarabine; D017035:Pravastatin; D015255:Idarubicin