PMID- 25540064
OWN - NLM
STAT- MEDLINE
DCOM- 20150818
LR  - 20221207
IS  - 1865-3774 (Electronic)
IS  - 0925-5710 (Linking)
VI  - 101
IP  - 2
DP  - 2015 Feb
TI  - A phase 1/2 study of bosutinib in Japanese adults with Philadelphia 
      chromosome-positive chronic myeloid leukemia.
PG  - 154-64
LID - 10.1007/s12185-014-1722-8 [doi]
AB  - This phase 1/2 study evaluated the safety and pharmacokinetics (part 1) and 
      efficacy and safety (part 2) of bosutinib in Japanese Philadelphia 
      chromosome-positive (Ph+) chronic-phase (CP) or advanced-phase chronic myeloid 
      leukemia (CML) patients resistant/intolerant to previous imatinib (2L) or 
      imatinib+dasatinib/nilotinib (3L). Based on dose-limiting toxicities and previous 
      studies, the part 2 bosutinib starting dose was 500 mg/day (n = 63). For CP CML 
      2L (n = 28), the cumulative major cytogenetic response (MCyR) rate by week 24 was 
      36 % (primary endpoint); the cumulative major molecular response (MMR) rate 
      through the study was 43 %. Transformation to accelerated/blast phase (AP/BP) was 
      observed in one patient. Progression-free survival (PFS) and overall survival 
      (OS) rates at 96 weeks were 94 and 96 %, respectively. Of seven advanced-phase 2L 
      patients, one had confirmed complete hematologic response at week 84, and one had 
      AP/BP transformation. PFS and OS rates at week 96 were 21 and 43 %. For 3L (n = 
      11), cumulative MCyR rate by week 24 was 18 %; cumulative MMR rate was 18 %; no 
      transformations occurred. Common non-hematologic adverse events (AEs) were 
      diarrhea (95 %), rash (57 %), and nasopharyngitis (51 %). Sixteen patients 
      discontinued due to adverse events; no deaths occurred within 30 days of the last 
      dose. Bosutinib 500 mg/day demonstrated efficacy and manageable toxicity in 
      Japanese Ph+ CML patients resistant/intolerant to imatinib.
FAU - Nakaseko, Chiaki
AU  - Nakaseko C
AD  - Department of Hematology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, 
      Chiba, 260-8677, Japan, chiaki-nakaseko@faculty.chiba-u.jp.
FAU - Takahashi, Naoto
AU  - Takahashi N
FAU - Ishizawa, Kenichi
AU  - Ishizawa K
FAU - Kobayashi, Yukio
AU  - Kobayashi Y
FAU - Ohashi, Kazuteru
AU  - Ohashi K
FAU - Nakagawa, Yasunori
AU  - Nakagawa Y
FAU - Yamamoto, Kazuhito
AU  - Yamamoto K
FAU - Miyamura, Koichi
AU  - Miyamura K
FAU - Taniwaki, Masafumi
AU  - Taniwaki M
FAU - Okada, Masaya
AU  - Okada M
FAU - Kawaguchi, Tatsuya
AU  - Kawaguchi T
FAU - Shibata, Atsushi
AU  - Shibata A
FAU - Fujii, Yosuke
AU  - Fujii Y
FAU - Ono, Chiho
AU  - Ono C
FAU - Ohnishi, Kazunori
AU  - Ohnishi K
LA  - eng
SI  - ClinicalTrials.gov/NCT00811070
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141225
PL  - Japan
TA  - Int J Hematol
JT  - International journal of hematology
JID - 9111627
RN  - 0 (Aniline Compounds)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Nitriles)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinolines)
RN  - 5018V4AEZ0 (bosutinib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aniline Compounds/pharmacology/*therapeutic use
MH  - Antineoplastic Agents/pharmacology/*therapeutic use
MH  - Asian People
MH  - Disease Progression
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Japan
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug 
      therapy/*genetics/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Nitriles/pharmacology/*therapeutic use
MH  - *Philadelphia Chromosome
MH  - Protein Kinase Inhibitors/pharmacology/*therapeutic use
MH  - Quinolines/pharmacology/*therapeutic use
MH  - Retreatment
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2014/12/30 06:00
MHDA- 2015/08/19 06:00
CRDT- 2014/12/26 06:00
PHST- 2014/05/08 00:00 [received]
PHST- 2014/12/08 00:00 [accepted]
PHST- 2014/12/05 00:00 [revised]
PHST- 2014/12/26 06:00 [entrez]
PHST- 2014/12/30 06:00 [pubmed]
PHST- 2015/08/19 06:00 [medline]
AID - 10.1007/s12185-014-1722-8 [doi]
PST - ppublish
SO  - Int J Hematol. 2015 Feb;101(2):154-64. doi: 10.1007/s12185-014-1722-8. Epub 2014 
      Dec 25.