title: Concurrent use of proton pump inhibitors or H2 blockers did not adversely affect nilotinib efficacy in patients with chronic myeloid leukemia.
abstract: OBJECTIVE
  The impact of proton pump inhibitors (PPIs) and histamine H2 receptor antagonists (H2 blockers) on the efficacy of nilotinib was evaluated.
  
  
  METHODS
  Retrospective analyses were performed in patients with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP; N = 492) and in patients with imatinib-resistant or imatinib-intolerant Ph+ CML-CP (N = 256) treated with nilotinib.
  
  
  RESULTS
  In the newly diagnosed population, 87 (17.7 %) and 49 (10.0 %) patients received PPIs and H2 blockers, respectively. Major molecular response at 12 months was achieved by 59 (49.6 %) patients who received at least one PPI or H2 blocker (n = 119) and 153 (41.0 %) patients who did not receive any comedication (n = 373; P = 0.13). PPIs and H2 blockers were used by 77 (30.1 %) and 17 (6.6 %) patients with imatinib-resistant or imatinib-intolerant CML-CP, respectively. Major cytogenetic response by 12 months was achieved by 55 (64.0 %) patients who received at least one PPI or H2 blocker (n = 86) versus 98 (57.6 %) patients who did not receive any comedication (n = 170; P = 0.40); 39 (45.3 %) versus 65 (38.2 %), respectively, achieved complete cytogenetic response by 12 months (P = 0.34). Similar findings were observed in patients who received comedication for >50 % of the time on nilotinib therapy. Nilotinib steady-state trough concentration was not affected by the presence of PPIs or H2 blockers.
  
  
  CONCLUSIONS
  Concurrent use of PPIs or H2 blockers did not affect the pharmacokinetics and efficacy of nilotinib in patients with Ph+ CML-CP.
authors.affiliation: Oncology Clinical Pharmacology, Novartis Pharmaceuticals Corporation, Florham Park, NJ 07932, USA. ophelia.yin@novartis.com
authors.forename: Ophelia Q P
authors.initials: OQ
authors.lastname: Yin
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Giles
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Philipp
authors.initials: P
authors.lastname: le Coutre
authors.forename: Ovidiu
authors.initials: O
authors.lastname: Chiparus
authors.forename: Neil
authors.initials: N
authors.lastname: Gallagher
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Hughes
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors; D011743:Pyrimidines; C498826:nilotinib