PMID- 18347007
OWN - NLM
STAT- MEDLINE
DCOM- 20080505
LR  - 20220310
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 26
IP  - 11
DP  - 2008 Apr 10
TI  - Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase 
      inhibitor, in patients with metastatic breast cancer previously treated with an 
      anthracycline and a taxane.
PG  - 1810-6
LID - 10.1200/JCO.2007.14.5375 [doi]
AB  - PURPOSE: Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that 
      inhibits vascular endothelial growth factor receptor (VEGFR), platelet-derived 
      growth factor receptor, stem cell factor receptor (KIT), and colony-stimulating 
      factor-1 receptor. This phase II, open-label, multicenter study evaluated 
      sunitinib monotherapy in patients with metastatic breast cancer (MBC). PATIENTS 
      AND METHODS: Sixty-four patients previously treated with an anthracycline and a 
      taxane received sunitinib 50 mg/d in 6-week cycles (4 weeks on, then 2 weeks off 
      treatment). The primary end point was objective response rate. Plasma samples 
      were obtained for pharmacokinetic and biomarker analysis. RESULTS: Seven patients 
      achieved a partial response (median duration, 19 weeks), giving an overall 
      response rate of 11%. Three additional patients (5%) maintained stable disease 
      for >or= 6 months. Median time to progression and overall survival were 10 and 38 
      weeks, respectively. Notably, responses occurred in triple negative tumors and 
      HER2-positive, trastuzumab-treated patients. Thirty-three patients (52%) required 
      dose interruption during >or= 1 cycle, and 25 patients required dose reduction 
      (39%). Thirty-six patients (56%) had dose modifications due to adverse events 
      (AEs). Treatment was associated with increases in plasma VEGF and decreases in 
      soluble VEGFRs and KIT. The most common AEs were fatigue, nausea, diarrhea, 
      mucosal inflammation, and anorexia. Most AEs were mild to moderate (grade 1 to 2) 
      in severity and were effectively managed with dose delays or reductions. 
      CONCLUSION: Sunitinib is active in patients with heavily pretreated MBC. Most AEs 
      were of mild-to-moderate severity and manageable with supportive treatment and/or 
      dose modification. Further studies in breast cancer are warranted.
FAU - Burstein, Harold J
AU  - Burstein HJ
AD  - Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA. 
      hburstein@partners.org
FAU - Elias, Anthony D
AU  - Elias AD
FAU - Rugo, Hope S
AU  - Rugo HS
FAU - Cobleigh, Melody A
AU  - Cobleigh MA
FAU - Wolff, Antonio C
AU  - Wolff AC
FAU - Eisenberg, Peter D
AU  - Eisenberg PD
FAU - Lehman, Mary
AU  - Lehman M
FAU - Adams, Bonne J
AU  - Adams BJ
FAU - Bello, Carlo L
AU  - Bello CL
FAU - DePrimo, Samuel E
AU  - DePrimo SE
FAU - Baum, Charles M
AU  - Baum CM
FAU - Miller, Kathy D
AU  - Miller KD
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
DEP - 20080317
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Anthracyclines)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Bridged-Ring Compounds)
RN  - 0 (Indoles)
RN  - 0 (Pyrroles)
RN  - 0 (Taxoids)
RN  - 1605-68-1 (taxane)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - V99T50803M (Sunitinib)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Anthracyclines/administration & dosage
MH  - Antineoplastic Agents/adverse effects/blood/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Biomarkers, Tumor/blood
MH  - Breast Neoplasms/blood/*drug therapy/mortality
MH  - Bridged-Ring Compounds/administration & dosage
MH  - Carcinoma/classification/*drug therapy/*secondary
MH  - Drug Administration Schedule
MH  - Fatigue/chemically induced
MH  - Female
MH  - Gastrointestinal Diseases/chemically induced
MH  - Hematologic Diseases/chemically induced
MH  - Humans
MH  - Indoles/adverse effects/blood/*therapeutic use
MH  - Middle Aged
MH  - Protein-Tyrosine Kinases/*antagonists & inhibitors
MH  - Pyrroles/adverse effects/blood/*therapeutic use
MH  - Sunitinib
MH  - Survival Rate
MH  - Taxoids/administration & dosage
EDAT- 2008/03/19 09:00
MHDA- 2008/05/06 09:00
CRDT- 2008/03/19 09:00
PHST- 2008/03/19 09:00 [pubmed]
PHST- 2008/05/06 09:00 [medline]
PHST- 2008/03/19 09:00 [entrez]
AID - JCO.2007.14.5375 [pii]
AID - 10.1200/JCO.2007.14.5375 [doi]
PST - ppublish
SO  - J Clin Oncol. 2008 Apr 10;26(11):1810-6. doi: 10.1200/JCO.2007.14.5375. Epub 2008 
      Mar 17.