Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group.
OBJECTIVE
Several phase II studies have suggested that cytarabine (AraC) was not required in the treatment of newly diagnosed acute promyelocytic leukemia (APL) patients receiving all-trans-retinoic acid (ATRA), an anthracycline, and maintenance therapy, and we aimed at confirming this finding in a randomized trial.


METHODS
Newly diagnosed APL patients younger than age 60 years with a WBC count of less than 10,000/microL were randomly assigned to receive either ATRA combined with and followed by three daunorubicin (DNR) plus AraC courses and a 2-year maintenance regimen (AraC group) or the same treatment but without AraC (no AraC group). Patients older than age 60 years and patients with initial WBC count of more than 10,000/microL were not randomly assigned but received risk-adapted treatment, with higher dose of AraC and CNS prophylaxis in patients with WBC counts more than 10,000/microL.


RESULTS
Overall, 328 (96.5%) of 340 patients achieved complete remission (CR). In the AraC and the no AraC groups, the CR rates were 99% and 94% (P = .12), the 2-year cumulative incidence of relapse (CIR) rates were 4.7% and 15.9% (P = .011), the event-free survival (EFS) rates were 93.3% and 77.2% (P = .0021), and survival rates were 97.9% and 89.6% (P = .0066), respectively. In patients younger than age 60 years with WBC counts more than 10,000/microL, the CR, 2-year CIR, EFS, and survival rates were 97.3%, 2.9%, 89%, and 91.9%, respectively.


CONCLUSIONS
These results support a role for AraC in addition to ATRA and anthracyclines in the treatment of newly diagnosed APL, at least using DNR at the cumulative dose we used and with the consolidation and maintenance regimens we used.
Adès
Lionel
L
Assistance Publique-Hôpitaux de Paris, Hôpital Avicenne, Service d'Hématologie Clinique, Paris 13 University, Bobigny, France.
Chevret
Sylvie
S
Raffoux
Emmanuel
E
de Botton
Stephane
S
Guerci
Agnes
A
Pigneux
Arnaud
A
Stoppa
Anne Marie
AM
Lamy
Thierry
T
Rigal-Huguet
Francoise
F
Vekhoff
Anne
A
Meyer-Monard
Sandrine
S
Maloisel
Frederic
F
Deconinck
Eric
E
Ferrant
Augustin
A
Thomas
Xavier
X
Fegueux
Nathalie
N
Chomienne
Christine
C
Dombret
Herve
H
Degos
Laurent
L
Fenaux
Pierre
P
D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000627:therapeutic use*; D003630:Daunorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D016019:Survival Analysis; D014212:Tretinoin / Q000008:administration & dosage
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D014212:Tretinoin; D003630:Daunorubicin