title: Nilotinib for the frontline treatment of Ph(+) chronic myeloid leukemia.
abstract: 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.
authors.affiliation: Department of Hematology-Oncology, L. and A. Seràgnoli, University of Bologna, S. Orsola-Malpighi Hospital, 40138 Bologna, Italy. gianantonio.rosti@unibo.it
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Rosti
authors.forename: Francesca
authors.initials: F
authors.lastname: Palandri
authors.forename: Fausto
authors.initials: F
authors.lastname: Castagnetti
authors.forename: Massimo
authors.initials: M
authors.lastname: Breccia
authors.forename: Luciano
authors.initials: L
authors.lastname: Levato
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gugliotta
authors.forename: Adele
authors.initials: A
authors.lastname: Capucci
authors.forename: Michele
authors.initials: M
authors.lastname: Cedrone
authors.forename: Carmen
authors.initials: C
authors.lastname: Fava
authors.forename: Tamara
authors.initials: T
authors.lastname: Intermesoli
authors.forename: Giovanna Rege
authors.initials: GR
authors.lastname: Cambrin
authors.forename: Fabio
authors.initials: F
authors.lastname: Stagno
authors.forename: Mario
authors.initials: M
authors.lastname: Tiribelli
authors.forename: Marilina
authors.initials: M
authors.lastname: Amabile
authors.forename: Simona
authors.initials: S
authors.lastname: Luatti
authors.forename: Angela
authors.initials: A
authors.lastname: Poerio
authors.forename: Simona
authors.initials: S
authors.lastname: Soverini
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Testoni
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Giuliana
authors.initials: G
authors.lastname: Alimena
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Pane
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib