PMID- 20959830
OWN - NLM
STAT- MEDLINE
DCOM- 20110301
LR  - 20240404
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 103
IP  - 10
DP  - 2010 Nov 9
TI  - Phase Ib study of CP-868,596, a PDGFR inhibitor, combined with docetaxel with or 
      without axitinib, a VEGFR inhibitor.
PG  - 1554-61
LID - 10.1038/sj.bjc.6605941 [doi]
AB  - BACKGROUND: Tumoural interstitial hypertension, possibly modulated by 
      platelet-derived and vascular endothelial growth factor receptors (PDGFR and 
      VEGFR), may mediate resistance to chemotherapy. METHODS: Forty-eight patients 
      with advanced solid tumours received oral PDGFR inhibitor CP-868,596 (60-100 mg 
      twice daily (BID)) and docetaxel (75-100 mg m(-)(2)), or CP-868,596 (60 mg BID), 
      docetaxel (75 mg m(-)(2)), and VEGFR inhibitor axitinib (5 mg BID). RESULTS: The 
      CP-868,596/docetaxel was escalated as above. The CP-868,596/docetaxel/axitinib 
      was not dose escalated because of increased incidence of mucositis-like adverse 
      events (AEs) with concurrent neutropenia relative to that expected for docetaxel. 
      All tested regimens were tolerable, including 100 mg BID CP-868,596 (recommended 
      phase II dose) plus 100 mg m(-)(2) docetaxel (maximum approved dose). Most 
      treatment-emergent AEs were mild-moderate and reversible, commonly including 
      nausea, diarrhoea, vomiting, constipation, fatigue, and anaemia 
      (CP-868,596/docetaxel), and hypertension, lethargy, diarrhoea, and fatigue 
      (CP-868,596/docetaxel/axitnib). Pharmacokinetics were unaffected by 
      co-administration. Twenty-one patients achieved stable disease, including all 
      seven evaluable on CP-868,596/docetaxel/axitinib. All nine 
      CP-868,596/docetaxel/axitinib patients received therapy for a median of six 
      (range, 3-16) cycles. CONCLUSIONS: The CP-868,596/docetaxel was well tolerated, 
      but increased efficacy was not observed. Addition of axitinib delivered greater 
      benefits than expected in the number of patients achieving prolonged stable 
      disease with a moderate increase in AEs.
FAU - Michael, M
AU  - Michael M
AD  - Peter MacCallum Cancer Centre, Consultant Medical Oncologist, Division of 
      Haematology and Medical Oncology, Chair of GI Clinical Service, Locked Bag 1, 
      A'Beckett Street, Victoria 8006, Australia. Michael.Michael@petermac.org
FAU - Vlahovic, G
AU  - Vlahovic G
FAU - Khamly, K
AU  - Khamly K
FAU - Pierce, K J
AU  - Pierce KJ
FAU - Guo, F
AU  - Guo F
FAU - Olszanski, A J
AU  - Olszanski AJ
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20101019
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (Indazoles)
RN  - 0 (Taxoids)
RN  - 15H5577CQD (Docetaxel)
RN  - AYI8EX34EU (Creatinine)
RN  - C9LVQ0YUXG (Axitinib)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
RN  - RFM9X3LJ49 (Bilirubin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Angiogenesis Inhibitors/adverse effects/therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Axitinib
MH  - Bilirubin/blood
MH  - Creatinine/blood
MH  - Docetaxel
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Imidazoles/adverse effects/therapeutic use
MH  - Indazoles/adverse effects/therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Neoplasms/blood/*drug therapy/pathology/surgery
MH  - Patient Selection
MH  - Receptors, Vascular Endothelial Growth Factor/*antagonists & 
      inhibitors/pharmacokinetics
MH  - Taxoids/adverse effects
PMC - PMC2990584
EDAT- 2010/10/21 06:00
MHDA- 2011/03/02 06:00
PMCR- 2011/11/09
CRDT- 2010/10/21 06:00
PHST- 2010/10/21 06:00 [entrez]
PHST- 2010/10/21 06:00 [pubmed]
PHST- 2011/03/02 06:00 [medline]
PHST- 2011/11/09 00:00 [pmc-release]
AID - 6605941 [pii]
AID - 10.1038/sj.bjc.6605941 [doi]
PST - ppublish
SO  - Br J Cancer. 2010 Nov 9;103(10):1554-61. doi: 10.1038/sj.bjc.6605941. Epub 2010 
      Oct 19.