Study protocol of the RAND-study: a multicenter, prospective cohort study investigating response and adherence to nilotinib treatment in chronic myeloid leukemia.
BACKGROUND
The antitumor drug nilotinib has a large inter- and intra individual variability in pharmacokinetics. Adherence to treatment may substantially influence plasma levels and has been recognized as the most important determinant of treatment failure in chronic myeloid leukemia (CML). A better understanding of the various factors contributing to the efficacy of treatment is essential for the development of interventions to optimize the treatment of chronic phase CML (CP-CML) with a protein kinase inhibitor like nilotinib.


METHODS
In this multicenter prospective observational cohort study 70 adult patients with CP-CML starting treatment with nilotinib will be followed up for at least 12 months. Response to treatment is evaluated after 3, 6 and 12 months. Adherence is primarily assessed by counting the daily intake of nilotinib capsules by means of a medication event monitoring system (MEMS). Before the start of nilotinib treatment and after 3, 6 and 12 months, patients are asked to fill in a comprehensive questionnaire including topics on quality of life, side effects, attitude towards disease and medication, the patients' appreciation of information received about the medication, and discontinuation, and trough plasma levels of nilotinib are measured.


CONCLUSIONS
The present study aims to get more insight into the efficacy of treatment with nilotinib and the various aspects that govern optimal response, of which adherence is a primary endpoint. We hypothesize that patients who experience inadequate response levels to nilotinib are less adherent. In addition, their plasma levels of nilotinib may be lower. We expect that our findings will be useful for health care professionals to support patients with the use of nilotinib in order to derive optimal benefit from their medication.


BACKGROUND
Netherlands Trial Registry NTR3992.
Department of Clinical Pharmacology and Pharmacy, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. c.boons@vumc.nl.
Christel C L M
CC
Boons
Eleonora L
EL
Swart
Lonneke
L
Timmers
Peter M
PM
van de Ven
Jeroen J W M
JJ
Janssen
Jacqueline G
JG
Hugtenburg
D059788:Dried Blood Spot Testing; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D055118:Medication Adherence; D009426:Netherlands; D010361:Patients; D011446:Prospective Studies; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D011743:Pyrimidines; C498826:nilotinib