PMID- 25290090
OWN - NLM
STAT- MEDLINE
DCOM- 20150126
LR  - 20211021
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 111
IP  - 11
DP  - 2014 Nov 25
TI  - Bosutinib plus capecitabine for selected advanced solid tumours: results of a 
      phase 1 dose-escalation study.
PG  - 2058-66
LID - 10.1038/bjc.2014.508 [doi]
AB  - BACKGROUND: This phase 1 study evaluated the maximum tolerated dose (MTD), 
      safety, and efficacy of bosutinib (competitive Src/Abl tyrosine kinase inhibitor) 
      plus capecitabine. METHODS: Patients with locally advanced/metastatic breast, 
      pancreatic, or colorectal cancers; cholangiocarcinoma; or glioblastoma received 
      bosutinib plus capecitabine at eight of nine possible dose combinations using an 
      'up-down' design to determine the toxicity contour of the combination. RESULTS: 
      Among 32 enrolled patients, none of the 9 patients receiving MTD (bosutinib 300 
      mg once daily plus capecitabine 1000 mg m(-2) twice daily) experienced 
      dose-limiting toxicities (DLTs). Overall, 2 out of 31 (6%) evaluable patients 
      experienced DLTs (grade 3 neurologic pain (n=1); grade 3 pruritus/rash and 
      increased alanine aminotransferase (n=1)). Most common treatment-related adverse 
      events (AEs) were diarrhoea, nausea, vomiting, palmar-plantar erythrodysesthesia 
      (PPE), fatigue; most frequent grade 3/4 AEs: PPE, fatigue, and increased 
      alanine/aspartate aminotransferase. Although diarrhoea was common, 91% of 
      affected patients experienced maximum grade 1/2 events that resolved. Best 
      overall confirmed partial response or stable disease >24 weeks (all tumour types) 
      was observed in 6 and 13% of patients. CONCLUSIONS: In this population of 
      patients with advanced solid tumours, bosutinib plus capecitabine demonstrated a 
      safety profile similar to that previously reported for bosutinib or capecitabine 
      monotherapy; limited efficacy was observed.
FAU - Isakoff, S J
AU  - Isakoff SJ
AD  - Division of Hematology and Oncology, Massachusetts General Hospital Cancer 
      Center, and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
FAU - Wang, D
AU  - Wang D
AD  - Phase I Clinical Trials Program, Henry Ford Hospital, 2799 West Grand Boulevard, 
      Detroit, MI 48202, USA.
FAU - Campone, M
AU  - Campone M
AD  - Institut de Cancerologie de l'Quest-Rene Gauducheau, Saint Herblain, Nantes Cedex 
      44805, France.
FAU - Calles, A
AU  - Calles A
AD  - START Madrid, Centro Integral Oncologico Clara Campal, Hospital Madrid 
      Norte-Sanchinarro, C/Ona n degrees 10, 28050 Madrid, Spain.
FAU - Leip, E
AU  - Leip E
AD  - Oncology Clinical Statistics, Pfizer Inc, 10 Fawcett Street, Suite 2013, 
      Cambridge, MA 02138, USA.
FAU - Turnbull, K
AU  - Turnbull K
AD  - Oncology Clinical Development, Pfizer Inc, 10 Fawcett Street, Suite 2013, 
      Cambridge, MA 02138, USA.
FAU - Bardy-Bouxin, N
AU  - Bardy-Bouxin N
AD  - Oncology Late Phase Strategy Development, Pfizer Global Research and Development, 
      23-25 av du Dr Lannelongue, Paris 75668, France.
FAU - Duvillie, L
AU  - Duvillie L
AD  - Oncology Clinical Development, Pfizer Global Research and Development, 23-25 av 
      du Dr Lannelongue, Paris 75668, France.
FAU - Calvo, E
AU  - Calvo E
AD  - START Madrid, Centro Integral Oncologico Clara Campal, Hospital Madrid 
      Norte-Sanchinarro, C/Ona n degrees 10, 28050 Madrid, Spain.
LA  - eng
SI  - ClinicalTrials.gov/NCT00959946
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20141007
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Aniline Compounds)
RN  - 0 (Nitriles)
RN  - 0 (Quinolines)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 5018V4AEZ0 (bosutinib)
RN  - 6804DJ8Z9U (Capecitabine)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Aniline Compounds/administration & dosage/adverse effects
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Capecitabine
MH  - Deoxycytidine/administration & dosage/adverse effects/analogs & derivatives
MH  - Female
MH  - Fluorouracil/administration & dosage/adverse effects/analogs & derivatives
MH  - Humans
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Neoplasms/*drug therapy/pathology
MH  - Nitriles/administration & dosage/adverse effects
MH  - Quinolines/administration & dosage/adverse effects
PMC - PMC4260032
EDAT- 2014/10/08 06:00
MHDA- 2015/01/27 06:00
PMCR- 2014/11/25
CRDT- 2014/10/08 06:00
PHST- 2013/12/23 00:00 [received]
PHST- 2014/07/01 00:00 [revised]
PHST- 2014/08/25 00:00 [accepted]
PHST- 2014/10/08 06:00 [entrez]
PHST- 2014/10/08 06:00 [pubmed]
PHST- 2015/01/27 06:00 [medline]
PHST- 2014/11/25 00:00 [pmc-release]
AID - bjc2014508 [pii]
AID - 10.1038/bjc.2014.508 [doi]
PST - ppublish
SO  - Br J Cancer. 2014 Nov 25;111(11):2058-66. doi: 10.1038/bjc.2014.508. Epub 2014 
      Oct 7.