title: 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.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA. hburstein@partners.org
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Burstein
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Elias
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
authors.forename: Melody A
authors.initials: MA
authors.lastname: Cobleigh
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Wolff
authors.forename: Peter D
authors.initials: PD
authors.lastname: Eisenberg
authors.forename: Mary
authors.initials: M
authors.lastname: Lehman
authors.forename: Bonne J
authors.initials: BJ
authors.lastname: Adams
authors.forename: Carlo L
authors.initials: CL
authors.lastname: Bello
authors.forename: Samuel E
authors.initials: SE
authors.lastname: DePrimo
authors.forename: Charles M
authors.initials: CM
authors.lastname: Baum
authors.forename: Kathy D
authors.initials: KD
authors.lastname: Miller
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D002277:Carcinoma / Q000145:classification / Q000188:drug therapy* / Q000556:secondary*; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D008875:Middle Aged; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011758:Pyrroles / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D000077210:Sunitinib; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D001952:Bridged-Ring Compounds; D007211:Indoles; D011758:Pyrroles; D043823:Taxoids; C080625:taxane; D011505:Protein-Tyrosine Kinases; D000077210:Sunitinib