Food-effect study of nilotinib in chronic myeloid leukaemia (NiFo study): Enabling dose reduction and relief of treatment burden

Christel C L M Boons, Yvonne M den Hartog, Jeroen J W M Janssen, Anthe S Zandvliet, René M Vos, Eleonora L Swart, N Harry Hendrikse, Jacqueline G Hugtenburg

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

OBJECTIVES: Taking advantage of its food-dependent bioavailability, the present study investigated the effect of a reduced dose taken with real-life meals on the pharmacokinetics (PK) of nilotinib in chronic myeloid leukaemia (CML) patients.

METHODS: Nilotinib was taken fasted (300 mg BID, days 1-4) or with real-life meals (200 mg BID, days 5-11). Rich sampling (days 1, 3, 8, 11) allowed for non-compartmental PK analysis. Nilotinib exposure (AUC0-12 h -Cmin -Cmax ) and its intra- and interpatient variability were compared between the two regimens. Adverse events were recorded by means of a patient diary and ECG monitoring.

RESULTS: Fifteen patients aged 40-74 years participated. Nilotinib PK following 200 mg BID taken with a meal strongly resembled that of 300 mg BID taken fasted (Cmin percentile (P)10-P90: 665-1404 ng/mL and 557-1743 ng/mL, respectively). Meals delayed nilotinib absorption. Intra- and interpatient variability were not increased by intake with meals. Nilotinib with food was well tolerated.

CONCLUSION: With support of therapeutic drug monitoring, the use of a reduced 200 mg nilotinib dose with real-life meals seems feasible and safe. Future (confirmatory) studies should further explore the usefulness of nilotinib dosing together with food, including the relationship with treatment efficacy as well as long-term effects on quality of life.

CLINICAL TRIAL REGISTRATION: NTR5000 (Netherlands Trial Register, www.trialregister.nl).

Original languageEnglish
Pages (from-to)148-155
Number of pages8
JournalEuropean Journal of Haematology
Volume105
Issue number2
DOIs
Publication statusPublished - 1 Aug 2020

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