Nilotinib for the frontline treatment of Ph(+) chronic myeloid leukemia.
Nilotinib has a higher binding affinity and selectivity for BCR-ABL with respect to imatinib and is an effective treatment of chronic myeloid leukemia (CML) after imatinib failure. In a phase 2 study, 73 early chronic-phase, untreated, Ph(+) CML patients, received nilotinib at a dose of 400 mg twice daily. The primary endpoint was the complete cytogenetic response (CCgR) rate at 1 year. With a median follow-up of 15 months, the CCgR rate at 1 year was 96%, and the major molecular response rate 85%. Responses were rapid, with 78% CCgR and 52% major molecular response at 3 months. During the first year, the treatment was interrupted at least once in 38 patients (52%). The mean daily dose ranged between 600 and 800 mg in 74% of patients, 400 and 599 mg in 18% of patients, and was less than 400 mg in 8% of patients. Dose interruptions were mainly due to nonhematologic and biochemical side effects. Myelosuppression was irrelevant. One patient progressed to blastic crisis after 6 months; one went off-treatment for lipase increase grade 4 (no pancreatitis). Nilotinib is safe and very active in early chronic-phase CML. These data support a role for nilotinib for the frontline treatment of CML. This study was registered at ClinicalTrials.gov as NCT00481052.
Rosti
Gianantonio
G
Department of Hematology-Oncology, L. and A. Seràgnoli, University of Bologna, S. Orsola-Malpighi Hospital, 40138 Bologna, Italy. gianantonio.rosti@unibo.it
Palandri
Francesca
F
Castagnetti
Fausto
F
Breccia
Massimo
M
Levato
Luciano
L
Gugliotta
Gabriele
G
Capucci
Adele
A
Cedrone
Michele
M
Fava
Carmen
C
Intermesoli
Tamara
T
Cambrin
Giovanna Rege
GR
Stagno
Fabio
F
Tiribelli
Mario
M
Amabile
Marilina
M
Luatti
Simona
S
Poerio
Angela
A
Soverini
Simona
S
Testoni
Nicoletta
N
Martinelli
Giovanni
G
Alimena
Giuliana
G
Pane
Fabrizio
F
Saglio
Giuseppe
G
Baccarani
Michele
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000187:drug effects; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents; D011743:Pyrimidines; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib