TY - JOUR
T1 - Food-effect study of nilotinib in chronic myeloid leukaemia (NiFo study)
T2 - Enabling dose reduction and relief of treatment burden
AU - Boons, Christel C L M
AU - den Hartog, Yvonne M
AU - Janssen, Jeroen J W M
AU - Zandvliet, Anthe S
AU - Vos, René M
AU - Swart, Eleonora L
AU - Hendrikse, N Harry
AU - Hugtenburg, Jacqueline G
N1 - © 2020 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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).
AB - 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).
KW - chronic myeloid leukaemia
KW - food effect
KW - nilotinib
KW - pharmacokinetics
KW - treatment burden
UR - http://www.scopus.com/inward/record.url?scp=85083441985&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/ejh.13418
DO - https://doi.org/10.1111/ejh.13418
M3 - Article
C2 - 32243653
SN - 0902-4441
VL - 105
SP - 148
EP - 155
JO - European journal of haematology
JF - European journal of haematology
IS - 2
ER -