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.
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.
Bolaños-Meade
Javier
J
University of Maryland Greenebaum Cancer Center, 22 South Greene Street, Room S9D07, Baltimore, MD 21201, USA.
Karp
Judith E
JE
Guo
Chuanfa
C
Sarkodee-Adoo
Clarence B
CB
Rapoport
Aaron P
AP
Tidwell
Michael L
ML
Buddharaju
Laxmi N
LN
Chen
T Timothy
TT
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
D003561:Cytarabine; D014212:Tretinoin; D005047:Etoposide; D015255:Idarubicin