title: An exploratory study of sunitinib in combination with docetaxel and trastuzumab as first-line therapy for HER2-positive metastatic breast cancer.
abstract: BACKGROUND
  This exploratory study assessed the safety, pharmacokinetics, and antitumor activity of sunitinib combined with docetaxel and trastuzumab.
  
  
  METHODS
  Patients with unresectable, locally recurrent or metastatic human epidermal growth factor receptor 2 (HER2)+ breast cancer received sunitinib plus docetaxel and trastuzumab. Sunitinib was administered at 37.5 mg/day for 2 weeks on treatment followed by 1 week off (Schedule 2/1). The primary endpoint was safety; secondary endpoints included pharmacokinetics and antitumor activity.
  
  
  RESULTS
  Twenty-six patients enrolled; 24 received at least one dose of sunitinib plus docetaxel and trastuzumab, and one patient received one dose of docetaxel and trastuzumab only. These 25 treated patients were evaluable for safety. Twenty-three patients discontinued the study, primarily due to disease progression. The planned dose of sunitinib was maintained in 10 patients and reduced at least once to 25 mg/day in 14 patients. The most common grade 3/4 non-hematologic adverse events were fatigue/asthenia (28%), diarrhea (16%), stomatitis (12%), vomiting (8%) and dyspnea (8%). Neutropenia was reported in all 24 evaluable patients; most events were grade 4. Three grade 1-3 cardiac adverse events occurred. Sunitinib and docetaxel levels were consistent with known single-agent levels, suggesting that there were no clinically relevant drug-drug interactions. Of 22 evaluable patients, 16 (73%) experienced an objective response (all confirmed partial responses).
  
  
  CONCLUSIONS
  Sunitinib combined with docetaxel and trastuzumab had an acceptable toxicity profile and showed preliminary antitumor activity as first-line treatment for metastatic HER2+ breast cancer.
authors.affiliation: Medical Oncology & Translational Research, Jules Bordet Institute, Boulevard de Waterloo, 125, 1000 Brussels, Belgium. fatimacardoso@fundacaochampalimaud.pt
authors.forename: Fatima
authors.initials: F
authors.lastname: Cardoso
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Canon
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
authors.forename: Daniela
authors.initials: D
authors.lastname: Aldrighetti
authors.forename: Jean-Pascal
authors.initials: JP
authors.lastname: Machiels
authors.forename: Yasmina
authors.initials: Y
authors.lastname: Bouko
authors.forename: Lev
authors.initials: L
authors.lastname: Verkh
authors.forename: Tiziana
authors.initials: T
authors.lastname: Usari
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Kern
authors.forename: Carla
authors.initials: C
authors.lastname: Giorgetti
authors.forename: Luc
authors.initials: L
authors.lastname: Dirix
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism; D011758:Pyrroles / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000077210:Sunitinib; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000077143:Docetaxel; D007211:Indoles; D011758:Pyrroles; D018719:Erb-b2 Receptor Tyrosine Kinases; D000077210:Sunitinib; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human