title: Nilotinib 300 mg twice daily: an academic single-arm study of newly diagnosed chronic phase chronic myeloid leukemia patients.
abstract: The introduction and the extended clinical use of nilotinib in the first-line treatment of chronic myeloid leukemia have been based on company-sponsored trials. Independent confirmations are extremely important. We report an investigator-sponsored study of nilotinib 300 mg twice daily in 130 chronic myeloid leukemia patients in early chronic phase. A deep molecular response was achieved in 46% (MR4.0) and 17% (MR4.5) of patients at 2 years; 58% of the enrolled patients achieved a MR4.0at least once, with a sustained MR4.0in 52% of them. With a median observation of 29 months (range 24-37 months), 77% of patients were still on treatment with nilotinib. The reasons for permanent discontinuation were: 3% progression, 5% failure or suboptimal response, 8% adverse events, 1% treatment-free remission, and 5% other reasons. Thirteen thrombotic arterial events were reported in 12 patients. A prospective evaluation of metabolic effects showed an increase of fasting glucose without significant variations of glycated hemoglobin, an increase of total cholesterol (both low density lipoprotein and high density lipoprotein fractions) and a decrease of triglycerides. This study confirms a high and rapid efficacy of nilotinib 300 mg twice daily and provides detailed information on the type and incidence of non-hematologic and metabolic adverse events (clinicaltrials.gov identifier: 01535391).
authors.affiliation: Institute of Hematology "L. and A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, "S. Orsola-Malpighi" University Hospital, University of Bologna, Italy fausto.castagnetti@unibo.it.
authors.forename: Fausto
authors.initials: F
authors.lastname: Castagnetti
authors.affiliation: Department of Cellular Biotechnologies and Hematology, "Sapienza" University of Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Breccia
authors.affiliation: Institute of Hematology "L. and A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, "S. Orsola-Malpighi" University Hospital, University of Bologna, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gugliotta
authors.affiliation: Hematology Unit, Azienda Ospedaliera "Bianchi-Melacrino-Morelli", Reggio Calabria, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Martino
authors.affiliation: Hematology Unit, Azienda Ospedaliera "Spedali Civili", Brescia, Italy.
authors.forename: Mariella
authors.initials: M
authors.lastname: D'Adda
authors.affiliation: Chair of Hematology, University of Catania, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Stagno
authors.affiliation: U.O. Ematologia I, IRCCS AOU S. Martino-IST, Genova, Italy.
authors.forename: Angelo Michele
authors.initials: AM
authors.lastname: Carella
authors.affiliation: Hematology Unit, Arcispedale Santa Maria Nuova, IRCCS, Reggio Emilia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Avanzini
authors.affiliation: Division of Hematology and BMT, Department of Experimental and Clinical Medical Sciences, Azienda Ospedaliero-Universitaria di Udine, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Tiribelli
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, Department of Hematology and Oncology, "G. da Saliceto" Hospital, Piacenza, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Trabacchi
authors.affiliation: Hematology and Stem Cell Transplantation Unit, Azienda Ospedaliera Ospedali Riuniti Marche Nord (AORMN), Pesaro, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Visani
authors.affiliation: Clinical Hematology Unit, IRCCS AOU S. Martino-IST, Genova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Gobbi
authors.affiliation: Hematology Unit, "Santa Maria delle Croci" Hospital, Ravenna, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Salvucci
authors.affiliation: Hematology Unit, "Pugliese-Ciaccio" Hospital, Catanzaro, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Levato
authors.affiliation: Hematology and Clinical Immunology Unit, University of Padova, Padova, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Binotto
authors.affiliation: Hematology Unit, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Foggia, Italy.
authors.forename: Silvana Franca
authors.initials: SF
authors.lastname: Capalbo
authors.affiliation: Institute of Hematology "L. and A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, "S. Orsola-Malpighi" University Hospital, University of Bologna, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Bochicchio
authors.affiliation: Institute of Hematology "L. and A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, "S. Orsola-Malpighi" University Hospital, University of Bologna, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Soverini
authors.affiliation: Institute of Hematology "L. and A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, "S. Orsola-Malpighi" University Hospital, University of Bologna, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Cavo
authors.affiliation: Institute of Hematology "L. and A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, "S. Orsola-Malpighi" University Hospital, University of Bologna, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.affiliation: Department of Cellular Biotechnologies and Hematology, "Sapienza" University of Rome, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Alimena
authors.affiliation: Chair of Hematology, Department of Biochemistry and Medical Biotechnologies, "Federico II" University, Napoli, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Pane
authors.affiliation: Chair of Hematology, Department of Clinical and Biological Sciences, "S. Luigi Gonzaga" University Hospital, University of Torino, Orbassano (TO), Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.affiliation: Institute of Hematology "L. and A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, "S. Orsola-Malpighi" University Hospital, University of Bologna, Italy.
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Rosti
authors.affiliation: Department of Hematology and Oncology "L. and A. Seràgnoli", University of Bologna, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D005260:Female; D006801:Humans; D015466:Leukemia, Myeloid, Chronic-Phase / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D012074:Remission Induction / Q000379:methods; D013927:Thrombosis / Q000139:chemically induced; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D014280:Triglycerides; D002784:Cholesterol; C498826:nilotinib