Randomized study of intensified anthracycline doses for induction and recombinant interleukin-2 for maintenance in patients with acute myeloid leukemia age 50 to 70 years: results of the ALFA-9801 study.
PURPOSE In patients with acute myeloid leukemia (AML), induction chemotherapy is based on standard doses of anthracyclines and cytarabine. High doses of cytarabine have been reported as being too toxic for patients older than age 50 years, but few studies have evaluated intensified doses of anthracyclines. PATIENTS AND METHODS In this randomized Acute Leukemia French Association 9801 (ALFA-9801) study, high doses of daunorubicin (DNR; 80 mg/m(2)/d x 3 days) or idarubicin (IDA4; 12 mg/m(2)/d x 4 days) were compared with standard doses of idarubicin (IDA3; 12 mg/m(2)/d x 3 days) for remission induction in patients age 50 to 70 years, with an event-free survival (EFS) end point. After two consolidation courses based on intermediate doses of cytarabine, patients in continuous remission were randomly assigned to receive or not receive maintenance therapy with recombinant interleukin-2 (rIL-2; 5 x 10(6) U/m(2) x 5 days each month) for a total duration of 12 months. A total of 468 patients entered the study (median age, 60 years). Results Overall complete remission rate was 77% with significant differences among the three randomization arms (83%, 78%, and 70% in the IDA3, IDA4, and DNR arms, respectively; P = .04). However, no significant differences were observed in relapse incidence, EFS, or overall survival among the three arms. In the 161 patients randomly assigned for maintenance therapy, no difference in outcome was observed between the rIL-2 and the no further treatment arms. CONCLUSION Neither intensification of anthracycline doses nor maintenance with rIL-2 showed a significant impact on AML course, at least as scheduled in this trial.
Pautas
Cecile
C
Centre Hospitalier de Versailles, Hôpital André Mignot, Service Hématologie et Oncologie, 177 rue de Versailles, 78150 Le Chesnay, France.
Merabet
Fatiha
F
Thomas
Xavier
X
Raffoux
Emmanuel
E
Gardin
Claude
C
Corm
Selim
S
Bourhis
Jean-Henri
JH
Reman
Oumedaly
O
Turlure
Pascal
P
Contentin
Nathalie
N
de Revel
Thierry
T
Rousselot
Philippe
P
Preudhomme
Claude
C
Bordessoule
Dominique
D
Fenaux
Pierre
P
Terré
Christine
C
Michallet
Mauricette
M
Dombret
Hervé
H
Chevret
Sylvie
S
Castaigne
Sylvie
S
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003630:Daunorubicin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage / Q000031:analogs & derivatives; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011994:Recombinant Proteins / Q000008:administration & dosage; D012008:Recurrence; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome
D007376:Interleukin-2; D011994:Recombinant Proteins; C082598:aldesleukin; D015255:Idarubicin; D003630:Daunorubicin