title: Timed sequential therapy of acute myelogenous leukemia in adults: a phase II study of retinoids in combination with the sequential administration of cytosine arabinoside, idarubicin and etoposide.
abstract: Clinical outcome in acute myeloid leukemia (AML) is unsatisfactory. One strategy to augment cytotoxicity is TST. All-trans retinoic acid (ATRA) down-regulates bcl-2 expression and heightens AML sensitivity to cytosine arabinoside (ara-C)-induced apoptosis in vitro. We designed a trial of ATRA plus ara-C-based TST in an attempt to enhance drug-induced apoptosis and clinical outcome. Between January 1998 and February 2000, 63 patients received induction TST (oral ATRA days 1-6, ara-C and idarubicin days 2-4, VP-16 days 9-11) followed by consolidation TST (ATRA, ara-C and idarubicin followed by a second ara-C infusion days 11-13). Complete remission (CR) was 60%, with higher rates for patients of <60 years (79%), de novo AML (70%), and non-adverse cytogenetics (81%). Median disease-free survival (DFS) for CR patients was 11.2 months (32% at 3+ years). For patients <60 years with de novo AML and non-adverse cytogenetics who underwent two-cycle TST, DFS was 67% at 3+ years. However, patients of age equal to 60 years and those with poor-risk disease features still have poor CR and DFS, despite the addition of ATRA.
authors.affiliation: University of Maryland Greenebaum Cancer Center, 22 South Greene Street, Room S9D07, Baltimore, MD 21201, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Bolaños-Meade
authors.forename: Judith E
authors.initials: JE
authors.lastname: Karp
authors.forename: Chuanfa
authors.initials: C
authors.lastname: Guo
authors.forename: Clarence B
authors.initials: CB
authors.lastname: Sarkodee-Adoo
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Rapoport
authors.forename: Michael L
authors.initials: ML
authors.lastname: Tidwell
authors.forename: Laxmi N
authors.initials: LN
authors.lastname: Buddharaju
authors.forename: T Timothy
authors.initials: TT
authors.lastname: Chen
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003561:Cytarabine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012074:Remission Induction / Q000379:methods; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage
chemical_list: D003561:Cytarabine; D014212:Tretinoin; D005047:Etoposide; D015255:Idarubicin