PMID- 24674874
OWN - NLM
STAT- MEDLINE
DCOM- 20150112
LR  - 20211021
IS  - 1549-490X (Electronic)
IS  - 1083-7159 (Print)
IS  - 1083-7159 (Linking)
VI  - 19
IP  - 4
DP  - 2014 Apr
TI  - Bosutinib in combination with the aromatase inhibitor letrozole: a phase II trial 
      in postmenopausal women evaluating first-line endocrine therapy in locally 
      advanced or metastatic hormone receptor-positive/HER2-negative breast cancer.
PG  - 348-9
LID - 10.1634/theoncologist.2014-0021 [doi]
AB  - BACKGROUND: Endocrine therapy resistance in hormone receptor-positive (HR+) 
      breast cancer (BC) may involve crosstalk between HRs and growth factor signaling 
      pathways. We evaluated bosutinib, a dual Src/Abl tyrosine kinase inhibitor that 
      has previously demonstrated some antitumor activity in BC, plus letrozole as 
      first-line endocrine therapy in locally advanced or metastatic HR+/HER2- BC. 
      METHODS; Sixteen postmenopausal women were enrolled in a phase II study 
      evaluating the safety/efficacy of bosutinib plus letrozole. In the single-arm 
      safety/dose-confirming lead-in (part 1), patients received oral bosutinib at 400 
      mg/day plus letrozole at 2.5 mg/day; adverse events (AEs) and dose-limiting 
      toxicities (DLTs) were monitored, and initial efficacy was assessed. A randomized 
      efficacy/safety phase (part 2) was planned to evaluate the combination versus 
      letrozole monotherapy. RESULTS: Fifteen of 16 subjects experienced 
      treatment-related AEs, most commonly diarrhea (69%). Treatment-related 
      hepatotoxicity AEs (primarily alanine aminotransferase [ALT] or aspartate 
      aminotransferase [AST] elevations) occurred in 6 of 16 patients (38%). Four of 15 
      evaluable patients (27%) experienced a DLT (grade 3/4 ALT/AST elevations, n = 2; 
      grade 3 rash, n = 1; grade 3 diarrhea or vomiting, n = 1), including 1 Hy's law 
      hepatotoxicity case. All DLTs resolved following treatment discontinuation. One 
      patient achieved confirmed partial response; one had stable disease for >24 
      weeks. Study termination occurred before part 2. CONCLUSION: The unfavorable 
      risk-benefit ratio did not warrant further investigation of bosutinib plus 
      letrozole.
FAU - Moy, Beverly
AU  - Moy B
AD  - Massachusetts General Hospital, Boston Massachusetts, USA;
FAU - Neven, Patrick
AU  - Neven P
FAU - Lebrun, Fabienne
AU  - Lebrun F
FAU - Bellet, Meritxell
AU  - Bellet M
FAU - Xu, Binghe
AU  - Xu B
FAU - Sarosiek, Tomasz
AU  - Sarosiek T
FAU - Chow, Louis
AU  - Chow L
FAU - Goss, Paul
AU  - Goss P
FAU - Zacharchuk, Charles
AU  - Zacharchuk C
FAU - Leip, Eric
AU  - Leip E
FAU - Turnbull, Kathleen
AU  - Turnbull K
FAU - Bardy-Bouxin, Nathalie
AU  - Bardy-Bouxin N
FAU - Duvillie, Ladan
AU  - Duvillie L
FAU - Lang, Istvan
AU  - Lang I
LA  - eng
SI  - ClinicalTrials.gov/NCT00880009
PT  - Clinical Trial, Phase II
PT  - Journal Article
DEP - 20140327
PL  - England
TA  - Oncologist
JT  - The oncologist
JID - 9607837
RN  - 0 (Aniline Compounds)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Aromatase Inhibitors)
RN  - 0 (Nitriles)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinolines)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Receptors, Progesterone)
RN  - 0 (Triazoles)
RN  - 5018V4AEZ0 (bosutinib)
RN  - 7LKK855W8I (Letrozole)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Aniline Compounds/adverse effects/*therapeutic use
MH  - Antineoplastic Agents/adverse effects/therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use
MH  - Aromatase Inhibitors/adverse effects/*therapeutic use
MH  - Breast Neoplasms/*drug therapy
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Letrozole
MH  - Nitriles/adverse effects/*therapeutic use
MH  - Postmenopause
MH  - Protein Kinase Inhibitors/adverse effects/therapeutic use
MH  - Quinolines/adverse effects/*therapeutic use
MH  - Receptor, ErbB-2/metabolism
MH  - Receptors, Estrogen/metabolism
MH  - Receptors, Progesterone/metabolism
MH  - Triazoles/adverse effects/*therapeutic use
PMC - PMC3983830
EDAT- 2014/03/29 06:00
MHDA- 2015/01/13 06:00
PMCR- 2014/03/27
CRDT- 2014/03/29 06:00
PHST- 2014/03/29 06:00 [entrez]
PHST- 2014/03/29 06:00 [pubmed]
PHST- 2015/01/13 06:00 [medline]
PHST- 2014/03/27 00:00 [pmc-release]
AID - theoncologist.2014-0021 [pii]
AID - T1421 [pii]
AID - 10.1634/theoncologist.2014-0021 [doi]
PST - ppublish
SO  - Oncologist. 2014 Apr;19(4):348-9. doi: 10.1634/theoncologist.2014-0021. Epub 2014 
      Mar 27.