PMID- 34673442
OWN - NLM
STAT- MEDLINE
DCOM- 20220112
LR  - 20220114
IS  - 1873-5835 (Electronic)
IS  - 0145-2126 (Linking)
VI  - 111
DP  - 2021 Dec
TI  - Efficacy and safety following bosutinib dose reduction in patients with 
      Philadelphia chromosome‒positive leukemias.
PG  - 106690
LID - S0145-2126(21)00191-0 [pii]
LID - 10.1016/j.leukres.2021.106690 [doi]
AB  - The recommended starting dose of bosutinib is 500 mg/day for chronic-phase (CP) 
      or accelerated-/blast-phase Philadelphia chromosome-positive (Ph+) chronic 
      myeloid leukemia (CML) resistant/intolerant to prior therapy. However, some 
      patients may require dose reductions to manage the occurrences of adverse events 
      (AEs). Bosutinib efficacy and safety were evaluated following dose reductions in 
      a phase I/II study of Ph+ patients with CP CML resistant/intolerant to imatinib 
      or imatinib plus dasatinib and/or nilotinib, and those with 
      accelerated-/blast-phase CML or acute lymphoblastic leukemia after at least 
      imatinib treatment. In all, 570 patients with >/=4 years' follow-up were included 
      in this analysis. Among 144 patients who dose-reduced to bosutinib 400 mg/day 
      (without reduction to 300 mg/day), 22 (15 %) had complete cytogenetic response 
      (CCyR) before and after reduction, 40 (28 %) initially achieved CCyR after 
      reduction, and 4 (3 %) only had CCyR before reduction. Among 95 patients who 
      dose-reduced to bosutinib 300 mg/day, 23 (24 %) had CCyR before and after 
      reduction, 13 (14 %) initially achieved CCyR after reduction, and 3 (3 %) only 
      had CCyR before reduction. Results were similar to matched controls who remained 
      on 500 mg/day, indicating dose reductions had not substantially affected 
      efficacy. The incidence of treatment-emergent AEs was lower after dose 
      reductions, particularly for gastrointestinal events. The incidence of 
      hematologic toxicities generally was similar before and after dose reduction. The 
      management of AEs with bosutinib through dose reduction can lead to 
      improved/maintained efficacy and better tolerability; still, approximately half 
      of patients on treatment at year 4 maintained a dose of >/=500 mg/day. 
      ClinicalTrials.gov: NCT00261846.
CI  - Copyright (c) 2021. Published by Elsevier Ltd.
FAU - Kota, Vamsi
AU  - Kota V
AD  - Georgia Cancer Center at Augusta University, Augusta, GA, USA. Electronic 
      address: vkota@augusta.edu.
FAU - Brummendorf, Tim H
AU  - Brummendorf TH
AD  - Universitatsklinikum Aachen, RWTH Aachen, Germany; Universitatsklinikum 
      Hamburg-Eppendorf, Hamburg, Germany.
FAU - Gambacorti-Passerini, Carlo
AU  - Gambacorti-Passerini C
AD  - University of Milano-Bicocca, Monza, Italy.
FAU - Lipton, Jeff H
AU  - Lipton JH
AD  - Princess Margaret Cancer Centre, Toronto, ON, Canada.
FAU - Kim, Dong-Wook
AU  - Kim DW
AD  - Seoul St. Mary's Hospital, Leukemia Research Institute, The Catholic University 
      of Korea, Seoul, Republic of Korea.
FAU - An, Fiona
AU  - An F
AD  - Pfizer Inc, New York, NY, USA.
FAU - Leip, Eric
AU  - Leip E
AD  - Pfizer Inc, Cambridge, MA, USA.
FAU - Crescenzo, Rocco J
AU  - Crescenzo RJ
AD  - Pfizer Inc, Collegeville, PA, USA.
FAU - Ferdinand, Roxanne
AU  - Ferdinand R
AD  - Pfizer Inc, Tadworth, UK.
FAU - Cortes, Jorge E
AU  - Cortes JE
AD  - University of Texas MD Anderson Cancer Center, Houston, TX, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT00261846
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20210821
PL  - England
TA  - Leuk Res
JT  - Leukemia research
JID - 7706787
RN  - 0 (Aniline Compounds)
RN  - 0 (Nitriles)
RN  - 0 (Pyrimidines)
RN  - 0 (Quinolines)
RN  - 5018V4AEZ0 (bosutinib)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - F41401512X (nilotinib)
RN  - RBZ1571X5H (Dasatinib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Aniline Compounds/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Dasatinib/administration & dosage
MH  - *Drug Resistance, Neoplasm
MH  - Drug Tapering/*methods
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Imatinib Mesylate/administration & dosage
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy/pathology
MH  - Male
MH  - Middle Aged
MH  - Nitriles/administration & dosage
MH  - Philadelphia Chromosome
MH  - Prognosis
MH  - Pyrimidines/administration & dosage
MH  - Quinolines/administration & dosage
MH  - Retrospective Studies
MH  - Young Adult
OTO - NOTNLM
OT  - Bosutinib
OT  - Chronic myeloid leukemia
OT  - Dose modification
OT  - Dose reduction
EDAT- 2021/10/22 06:00
MHDA- 2022/01/13 06:00
CRDT- 2021/10/21 21:02
PHST- 2020/07/15 00:00 [received]
PHST- 2021/08/13 00:00 [revised]
PHST- 2021/08/19 00:00 [accepted]
PHST- 2021/10/22 06:00 [pubmed]
PHST- 2022/01/13 06:00 [medline]
PHST- 2021/10/21 21:02 [entrez]
AID - S0145-2126(21)00191-0 [pii]
AID - 10.1016/j.leukres.2021.106690 [doi]
PST - ppublish
SO  - Leuk Res. 2021 Dec;111:106690. doi: 10.1016/j.leukres.2021.106690. Epub 2021 Aug 
      21.