title: Safety and efficacy of switching to nilotinib 400 mg twice daily for patients with chronic myeloid leukemia in chronic phase with suboptimal response or failure on front-line imatinib or nilotinib 300 mg twice daily.
abstract: In a randomized, phase III trial of nilotinib versus imatinib in patients with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia in chronic phase, more patients had suboptimal response or treatment failure on front-line imatinib than on nilotinib. Patients with suboptimal response/treatment failure on imatinib 400 mg once or twice daily or nilotinib 300 mg twice daily could enter an extension study to receive nilotinib 400 mg twice daily. After a 19-month median follow up, the safety profile of nilotinib 400 mg twice daily in patients switching from imatinib (n=35) was consistent with previous reports, and few new adverse events occurred in patients escalating from nilotinib 300 mg twice daily (n=19). Of patients previously treated with imatinib or nilotinib 300 mg twice daily, respectively, 15 of 26 (58%) and 2 of 6 (33%) without complete cytogenetic response at extension study entry, and 11 of 34 (32%) and 7 of 18 (39%) without major molecular response at extension study entry, achieved these responses at any time on nilotinib 400 mg twice daily. Estimated 18-month rates of freedom from progression and overall survival after entering the extension study were lower for patients switched from imatinib (85% and 87%, respectively) versus nilotinib 300 mg twice daily (95% and 94%, respectively). Nilotinib dose escalation was generally well tolerated and improved responses in about one-third of patients with suboptimal response/treatment failure. Switch to nilotinib improved responses in some patients with suboptimal response/treatment failure on imatinib, but many did not achieve complete cytogenetic response (clinicaltrials.gov identifiers: 00718263, 00471497 - extension).
authors: South Australian Health and Medical Research Institute, University of Adelaide, Australia Division of Haematology and Centre for Cancer Biology, SA Pathology, Adelaide, Australia timothy.hughes@health.sa.gov.au.
authors: Timothy P
authors: TP
authors: Hughes
authors: Abteilung Hämatologie/Onkologie, Universitätsklinikum Jena, Germany.
authors: Andreas
authors: A
authors: Hochhaus
authors: The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Hagop M
authors: HM
authors: Kantarjian
authors: IDIBAPS, University of Barcelona, Spain.
authors: Francisco
authors: F
authors: Cervantes
authors: Inserm CIC 0802, CHU de Poitiers, France.
authors: François
authors: F
authors: Guilhot
authors: Division of Hematology and Oncology, University of Leipzig, Germany.
authors: Dietger
authors: D
authors: Niederwieser
authors: Charité - Universitätsmedizin Berlin, Germany.
authors: Philipp D
authors: PD
authors: le Coutre
authors: University of Bologna, Italy.
authors: Gianantonio
authors: G
authors: Rosti
authors: VU University Medical Center, Amsterdam, The Netherlands.
authors: Gert
authors: G
authors: Ossenkoppele
authors: HEMORIO, Rio de Janeiro, Brazil.
authors: Clarisse
authors: C
authors: Lobo
authors: Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Hirohiko
authors: H
authors: Shibayama
authors: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
authors: Xiaolin
authors: X
authors: Fan
authors: Novartis Pharma AG, Basel, Switzerland.
authors: Hans D
authors: HD
authors: Menssen
authors: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
authors: Charisse
authors: C
authors: Kemp
authors: The University of Chicago, IL, USA.
authors: Richard A
authors: RA
authors: Larson
authors: University of Turin, Orbassano, Italy.
authors: Giuseppe
authors: G
authors: Saglio
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides / Q000008:administration & dosage* / Q000009:adverse effects; D057915:Drug Substitution; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy*; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C498826:nilotinib