title: A phase I trial of two sequence-specific schedules of decitabine and vorinostat in patients with acute myeloid leukemia.
abstract: This phase I trial evaluated two schedules of escalating vorinostat in combination with decitabine every 28 days: (i) sequential or (ii) concurrent. There were three dose-limiting toxicities: grade 3 fatigue and generalized muscle weakness on the sequential schedule (n = 1) and grade 3 fatigue on the concurrent schedule (n = 2). The maximum tolerated dose was not reached on both planned schedules. The overall response rate (ORR) was 23% (three complete response [CR], two CR with incomplete incomplete blood count recovery [CRi], one partial response [PR] and two morphological leukemic free state [MLFS]). The ORR for all and previously untreated patients in the sequential arm was 13% (one CRi; one MLFS) and 0% compared to 30% (three CR; one CRi; one PR; one MLFS) and 36% in the concurrent arm (p = 0.26 for both), respectively. Decitabine plus vorinostat was safe and has clinical activity in patients with previously untreated acute myeloid leukemia. Responses appear higher with the concurrent dose schedule. Cumulative toxicities may limit long-term usage on the current dose/schedules.
authors: a Princess Margaret Phase I Consortium , Toronto , ON , Canada.
authors: Jonathan
authors: J
authors: How
authors: a Princess Margaret Phase I Consortium , Toronto , ON , Canada.
authors: Mark D
authors: MD
authors: Minden
authors: a Princess Margaret Phase I Consortium , Toronto , ON , Canada.
authors: Leber
authors: L
authors: Brian
authors: a Princess Margaret Phase I Consortium , Toronto , ON , Canada.
authors: Eric X
authors: EX
authors: Chen
authors: a Princess Margaret Phase I Consortium , Toronto , ON , Canada.
authors: Joseph
authors: J
authors: Brandwein
authors: a Princess Margaret Phase I Consortium , Toronto , ON , Canada.
authors: Andre C
authors: AC
authors: Schuh
authors: a Princess Margaret Phase I Consortium , Toronto , ON , Canada.
authors: Aaron D
authors: AD
authors: Schimmer
authors: a Princess Margaret Phase I Consortium , Toronto , ON , Canada.
authors: Vikas
authors: V
authors: Gupta
authors: a Princess Margaret Phase I Consortium , Toronto , ON , Canada.
authors: Sheila
authors: S
authors: Webster
authors: a Princess Margaret Phase I Consortium , Toronto , ON , Canada.
authors: Tammy
authors: T
authors: Degelder
authors: a Princess Margaret Phase I Consortium , Toronto , ON , Canada.
authors: Patricia
authors: P
authors: Haines
authors: a Princess Margaret Phase I Consortium , Toronto , ON , Canada.
authors: Lee-Anne
authors: LA
authors: Stayner
authors: a Princess Margaret Phase I Consortium , Toronto , ON , Canada.
authors: Shauna
authors: S
authors: McGill
authors: a Princess Margaret Phase I Consortium , Toronto , ON , Canada.
authors: Lisa
authors: L
authors: Wang
authors: b Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute , Bethesda , MD , USA.
authors: Richard
authors: R
authors: Piekarz
authors: a Princess Margaret Phase I Consortium , Toronto , ON , Canada.
authors: Tracy
authors: T
authors: Wong
authors: a Princess Margaret Phase I Consortium , Toronto , ON , Canada.
authors: Lillian L
authors: LL
authors: Siu
authors: b Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute , Bethesda , MD , USA.
authors: Igor
authors: I
authors: Espinoza-Delgado
authors: c Departments of Medicine and Pharmacology and Cancer Institute , University of Pittsburgh , Pittsburgh , PA , USA.
authors: Julianne L
authors: JL
authors: Holleran
authors: c Departments of Medicine and Pharmacology and Cancer Institute , University of Pittsburgh , Pittsburgh , PA , USA.
authors: Merrill J
authors: MJ
authors: Egorin
authors: a Princess Margaret Phase I Consortium , Toronto , ON , Canada.
authors: Karen W L
authors: KW
authors: Yee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000077209:Decitabine; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D012008:Recurrence; D012074:Remission Induction; D019233:Retreatment; D016896:Treatment Outcome; D000077337:Vorinostat
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat; D000077209:Decitabine; D001374:Azacitidine
keywords: Decitabine; acute myeloid leukemia; histone deacetylase inhibitor; hypomethylating agent; vorinostat