title: A retrospective study of the prescribing and outcomes of tyrosine kinase inhibitors in chronic myeloid leukaemia over a period of more than 10 years.
abstract: OBJECTIVE
  Since their introduction, tyrosine kinase inhibitors (TKIs) have been increasingly used in clinical practice. We describe the prescribing and the clinical and biological consequences of two such inhibitors, imatinib and erlotinib, in patients with chronic myeloid leukaemia (CML) in a practice setting over a period of more than 10 years.
  
  
  METHODS
  All patients who received at least one TKI for chronic phase CML between 2001 and 2012 in our university hospital were included in the study.
  
  
  CONCLUSIONS
  Of the 139 patients, with a median age of 57 years, who were surveyed, imatinib and nilotinib were prescribed as the first TKI in 131 (94%) and 8 (6%) patients, respectively. With a median follow-up of 6 years, 342 treatment modifications were observed: 113 (33%) increased doses, 109 (32%) decreased doses, 89 (26%) TKI changes, 14 (4%) definitive discontinuations, 13 (4%) temporary discontinuations and 4 (1%) additions of IFN-α. The main reasons for the 342 treatment modifications were adverse events (n = 112, 33%), long-term optimal response (n = 58, 17%) and failure (n = 57, 17%). Eighty-five (61%), 31 (22%), 18 (13%) and 5 (4%) patients had no, 1, 2 and 3 TKI changes, respectively. Imatinib was the most prescribed TKI (75%). Adverse events resulting in treatment modifications occurred in 18% of patients for imatinib, 49% for nilotinib and 41% for dasatinib (P < 0·001). Median time to TKI change whatever the reason was >50 months (not achieved) for imatinib, 22 months for nilotinib and 27 months for dasatinib (log-rank test, P < 0·001).
  
  
  CONCLUSIONS
  Imatinib was the most prescribed TKI both in the first and in subsequent therapeutic lines for chronic phase CML. Our study showed a very good efficacy-safety profile for imatinib at a median follow-up of 6 years in an unselected French population.
authors: Pharmacy Department, University Hospital, Dijon, France.
authors: A-S
authors: AS
authors: Lang
authors: Hematological Malignancies Registry, Burgundy University, Dijon, France.
authors: M
authors: M
authors: Mounier
authors: Hematology Department, University Hospital, Dijon, France.
authors: M
authors: M
authors: Roques
authors: Hematology Department, University Hospital, Dijon, France.
authors: M L
authors: ML
authors: Chretien
authors: Pharmacy Department, University Hospital, Dijon, France.
authors: M
authors: M
authors: Boulin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000069347:Erlotinib Hydrochloride / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006785:Hospitals, University; D006801:Humans; D000068877:Imatinib Mesylate / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010818:Practice Patterns, Physicians'; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate; D000069347:Erlotinib Hydrochloride
keywords: chronic myeloid leukaemia; efficacy; prescription practices; tolerance; tyrosine kinase inhibitors