PMID- 34195988
OWN - NLM
STAT- MEDLINE
DCOM- 20211220
LR  - 20211220
IS  - 1365-2141 (Electronic)
IS  - 0007-1048 (Linking)
VI  - 194
IP  - 2
DP  - 2021 Jul
TI  - Dasatinib dose optimisation based on therapeutic drug monitoring reduces pleural 
      effusion rates in chronic myeloid leukaemia patients.
PG  - 393-402
LID - 10.1111/bjh.17654 [doi]
AB  - Dasatinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor approved for 
      patients with chronic myeloid leukaemia (CML). Dasatinib 100 mg per day is 
      associated with an increased risk of pleural effusion (PlEff). We randomly 
      evaluated whether therapeutic drug monitoring (TDM) may reduce 
      dasatinib-associated significant adverse events (AEs) by 12 months (primary 
      endpoint). Eligible patients started dasatinib at 100 mg per day followed by 
      dasatinib (C)min assessment. Patients considered overdosed [(C)min >/= 3 nmol/l) 
      were randomised between a dose-reduction strategy (TDM arm) and standard of care 
      (control arm). Out of 287 evaluable patients, 80 patients were randomised. The 
      primary endpoint was not met due to early haematological AEs occurring before 
      effective dose reduction. However, a major reduction in the cumulative incidence 
      of PlEff was observed in the TDM arm compared to the control arm (4% vs. 15%; 11% 
      vs. 35% and 12% vs. 39% at one, two and three years, respectively (P = 0.0094)). 
      Molecular responses were superimposable in all arms. Dasatinib TDM during 
      treatment initiation was feasible and resulted in a significant reduction of the 
      incidence of PlEff in the long run, without impairing molecular responses. 
      (NCT01916785; https://clinicaltrials.gov).
CI  - (c) 2021 British Society for Haematology and John Wiley & Sons Ltd.
FAU - Rousselot, Philippe
AU  - Rousselot P
AUID- ORCID: 0000-0003-3238-4494
AD  - Department of Hematology and Oncology, Centre Hospitalier de Versailles, Le 
      Chesnay, France.
AD  - UMR1184, IDMIT Department Universite Paris-Saclay, Commissariat a l'energie 
      atomique et aux energies alternatives, University of Versailles 
      Saint-Quentin-en-Yvelines, Montigny-Le-Bretonneux, France.
FAU - Mollica, Luigina
AU  - Mollica L
AD  - Department of Hematology, Hopital Maisonneuve-Rosemont, University of Montreal, 
      Montreal, Quebec, Canada.
FAU - Guilhot, Joelle
AU  - Guilhot J
AD  - Inserm CIC 1402 CHU de Poitiers, Poitiers, France.
FAU - Guerci, Agnes
AU  - Guerci A
AD  - Department of Hematology, CHU Brabois Vandoeuvre, Nancy, France.
FAU - Nicolini, Franck E
AU  - Nicolini FE
AD  - Department of Hematology, Centre Leon Berard, Lyon, France.
FAU - Etienne, Gabriel
AU  - Etienne G
AUID- ORCID: 0000-0001-7600-4954
AD  - Department of Hematology, Institut Bergonie, Bordeaux, France.
FAU - Legros, Laurence
AU  - Legros L
AD  - Department of Hematology, Hopital Paul Brousse, Villejuif, France.
FAU - Charbonnier, Aude
AU  - Charbonnier A
AD  - Department of Hematology, Institut Paoli Calmette, Marseille, France.
FAU - Coiteux, Valerie
AU  - Coiteux V
AD  - Department of Hematology, Hopital Huriez - CHRU, Lille, France.
FAU - Dartigeas, Caroline
AU  - Dartigeas C
AD  - Department of Hematology, CHU de Tours, Tours, France.
FAU - Escoffre-Barbe, Martine
AU  - Escoffre-Barbe M
AD  - Department of Hematology, Centre Hospitalier Pontchaillou, Rennes, France.
FAU - Roy, Lydia
AU  - Roy L
AD  - Department of Hematology, Hopital Henri Mondor, AP-HP, Creteil, France.
FAU - Cony-Makhoul, Pascale
AU  - Cony-Makhoul P
AUID- ORCID: 0000-0002-1633-6479
AD  - Department of Hematology, Centre Hospitalier Annecy Genevois, Pringy, France.
FAU - Dubruille, Viviane
AU  - Dubruille V
AD  - Department of Hematology, Hopital Hotel-Dieu, CHU de Nantes, Nantes, France.
FAU - Gardembas, Martine
AU  - Gardembas M
AD  - Department of Hematology, CHU d'Angers, Angers, France.
FAU - Huguet, Francoise
AU  - Huguet F
AD  - Department of Hematology, Institut Universitaire du Cancer - Oncopole, Toulouse, 
      France.
FAU - Rea, Delphine
AU  - Rea D
AUID- ORCID: 0000-0001-5379-7461
AD  - Department of Hematology, Hopital Saint-Louis et EA3518, AP-HP, Paris, France.
FAU - Cayssials, Emilie
AU  - Cayssials E
AD  - Inserm CIC 1402 CHU de Poitiers, Poitiers, France.
AD  - Department of Hematology, CHU de Poitiers, Poitiers, France.
FAU - Guilhot, Francois
AU  - Guilhot F
AD  - Inserm CIC 1402 CHU de Poitiers, Poitiers, France.
FAU - Bergeron, Anne
AU  - Bergeron A
AUID- ORCID: 0000-0003-2156-254X
AD  - Department of Pneumology, Hopital Saint-Louis, AP-HP, Paris, France.
FAU - Molimard, Mathieu
AU  - Molimard M
AD  - Clinical Pharmacology Department, Centre Hospitalier Pellegrin, CHU de Bordeaux, 
      Bordeaux, France.
AD  - University of Bordeaux Segalen, Bordeaux, France.
FAU - Mahon, Francois-Xavier
AU  - Mahon FX
AD  - Department of Hematology, Institut Bergonie, Bordeaux, France.
AD  - University of Bordeaux Segalen, Bordeaux, France.
FAU - Cayuela, Jean-Michel
AU  - Cayuela JM
AD  - Hematology and Molecular Biology and EA3518, Hopital Saint-Louis, AP-HP, Paris, 
      France.
FAU - Busque, Lambert
AU  - Busque L
AD  - Department of Hematology, Hopital Maisonneuve-Rosemont, University of Montreal, 
      Montreal, Quebec, Canada.
FAU - Bouchet, Stephane
AU  - Bouchet S
AD  - Clinical Pharmacology Department, Centre Hospitalier Pellegrin, CHU de Bordeaux, 
      Bordeaux, France.
LA  - eng
SI  - ClinicalTrials.gov/NCT01916785
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210630
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - RBZ1571X5H (Dasatinib)
SB  - IM
CIN - Br J Haematol. 2021 Jul;194(2):234. PMID: 34195993
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use
MH  - Dasatinib/administration & dosage/adverse effects/*therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - *Drug Monitoring
MH  - Female
MH  - Humans
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Pleural Effusion/*chemically induced/prevention & control
MH  - Prospective Studies
MH  - Protein Kinase Inhibitors/administration & dosage/adverse effects/*therapeutic 
      use
MH  - Treatment Outcome
MH  - Young Adult
OTO - NOTNLM
OT  - chronic leukaemia
OT  - pharmacology
OT  - tyrosine kinases
EDAT- 2021/07/02 06:00
MHDA- 2021/12/21 06:00
CRDT- 2021/07/01 07:20
PHST- 2021/02/14 00:00 [received]
PHST- 2021/05/11 00:00 [accepted]
PHST- 2021/07/02 06:00 [pubmed]
PHST- 2021/12/21 06:00 [medline]
PHST- 2021/07/01 07:20 [entrez]
AID - 10.1111/bjh.17654 [doi]
PST - ppublish
SO  - Br J Haematol. 2021 Jul;194(2):393-402. doi: 10.1111/bjh.17654. Epub 2021 Jun 30.