Multicentre phase III trial on fludarabine, cytarabine (Ara-C), and idarubicin versus idarubicin, Ara-C and etoposide for induction treatment of younger, newly diagnosed acute myeloid leukaemia patients.
Fludarabine plus cytarabine (Ara-C) and idarubicin (FLAI) is an effective and well-tolerated induction regimen for the treatment of acute myeloid leukaemia (AML). This phase III trial compared the efficacy and toxicity of FLAI versus idarubicin plus Ara-C and etoposide (ICE) in 112 newly diagnosed AML patients <60 years. Fifty-seven patients received FLAI, as the first induction-remission course, and 55 patients received ICE. Post-induction treatment consisted of high-dose Ara-C (HDAC). After HDAC, patients in complete remission (CR) received a second consolidation course (mitoxantrone, etoposide, Ara-C) and autologous stem cell transplantation (auto-SCT) or allogeneic (allo)-SCT, according to the age, disease risk and donor availability. After a single induction course, CR rate was 74% in the FLAI arm and 51% in the ICE arm (P = 0.01), while death during induction was 2% and 9% respectively. Both haematological (P = 0.002) and non-haematological (P = 0.0001) toxicities, especially gastrointestinal (i.e. nausea, vomiting, mucositis and diarrhoea), were significantly lower in FLAI arm. In both arms, relapses were more frequent in patients who were not submitted to allo-SCT. After a median follow-up of 17 months, 30% and 38% of the patients are in continuous CR in FLAI and ICE arm respectively. Our prospective randomised study confirmed the anti-leukaemic effect and the low toxic profile of FLAI as induction treatment for newly diagnosed AML patients.
Russo
Domenico
D
Unit of Blood Diseases and Cell Therapy, Brescia University, Brescia, Italy. russo@med.unibs.it
Malagola
Michele
M
de Vivo
Antonio
A
Fiacchini
Mauro
M
Martinelli
Giovanni
G
Piccaluga
Pier P
PP
Damiani
Daniela
D
Candoni
Anna
A
Michielutti
Angela
A
Castelli
Maurizio
M
Testoni
Nicoletta
N
Ottaviani
Emanuela
E
Rondoni
Michela
M
Pricolo
Giancarla
G
Mazza
Patrizio
P
Zuffa
Eliana
E
Zaccaria
Alfonso
A
Raspadori
Donatella
D
Bocchia
Monica
M
Lauria
Francesco
F
Bonini
Alessandro
A
Avanzini
Paolo
P
Gugliotta
Luigi
L
Visani
Giuseppe
G
Fanin
Renato
R
Baccarani
Michele
M
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012074:Remission Induction; D033581:Stem Cell Transplantation; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
D003561:Cytarabine; D005047:Etoposide; D014740:Vidarabine; C024352:fludarabine; D015255:Idarubicin