Single cycle of arsenic trioxide-based consolidation chemotherapy spares anthracycline exposure in the primary management of acute promyelocytic leukemia.
PURPOSE Event-free survival following all-trans-retinoic acid (ATRA) -based therapy for acute promyelocytic leukemia (APL) averages 70% at 5 years. While arsenic trioxide (ATO) can induce remissions in 95% of relapsed patients, few studies have addressed the integration of ATO into the primary management of APL. This study examines the efficacy of a single cycle of ATO-based consolidation therapy in a treatment regimen designed to decrease exposure to other cytotoxic agents. PATIENTS AND METHODS After induction with ATRA and daunorubicin (DRN), untreated patients with APL received 3 days of cytarabine and DRN followed by 30 doses of ATO beginning on day 8. Molecular remitters received 2 years of risk-based maintenance therapy. Results Forty-one of 45 patients receiving induction therapy achieved remission; four patients died (one before treatment was initiated). Thirty-seven patients received consolidation and maintenance; of these one patient relapsed (CNS) and one died in remission during maintenance therapy (hepatic sickle cell crisis). With a median follow-up of 2.7 years, estimated disease-free survival was 90%; overall survival for all patients was 88%. Despite a total anthracycline dose of only 360 mg/m(2), cardiac ejection fraction decreased by > or = 20% in 20% of patients. CONCLUSION These data, combined with other recent studies using ATO in the primary management of APL, demonstrate the important role that ATO can play in the primary management of this curable disease. Future studies should continue to focus on reducing the toxicity of treatment without increasing the relapse rate.
Gore
Steven D
SD
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, CRB1-288, 1650 Orleans St, Baltimore, MD 21231, USA. gorest@jhmi.edu
Gojo
Ivana
I
Sekeres
Mikkael A
MA
Morris
Lawrence
L
Devetten
Marcel
M
Jamieson
Katarzyna
K
Redner
Robert L
RL
Arceci
Robert
R
Owoeye
Ibitayo
I
Dauses
Tianna
T
Schachter-Tokarz
Esther
E
Gallagher
Robert E
RE
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D010087:Oxides / Q000008:administration & dosage; D011379:Prognosis; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage; D055815:Young Adult
D001152:Arsenicals; D010087:Oxides; D003561:Cytarabine; D014212:Tretinoin; D000077237:Arsenic Trioxide; D003630:Daunorubicin