title: Phase II study of single-agent bosutinib, a Src/Abl tyrosine kinase inhibitor, in patients with locally advanced or metastatic breast cancer pretreated with chemotherapy.
abstract: BACKGROUND
  This phase II study evaluated single-agent bosutinib in pretreated patients with locally advanced or metastatic breast cancer.
  
  
  METHODS
  Patients received oral bosutinib 400 mg/day. The primary end point was the progression-free survival (PFS) rate at 16 weeks. Secondary end points included objective response rate, clinical benefit rate, 2-year overall survival rate, safety, and changes in levels of bone resorption/formation biomarkers.
  
  
  RESULTS
  Seventy-three patients were enrolled and treated. Median time from diagnosis of metastatic disease to initiation of bosutinib treatment was 24.5 months. For the intent-to-treat population, the PFS rate at 16 weeks was 39.6%. Unexpectedly, all responding patients (n = 4) were hormone receptor positive. The clinical benefit rate was 27.4%. The 2-year overall survival rate was 26.4%. The main toxic effects were diarrhea (66%), nausea (55%), and vomiting (47%). Grade 3-4 laboratory aminotransferase elevations occurred in 14 (19%) patients. Myelosuppression was minimal. No consistent changes in the levels of bone resorption/formation biomarkers were seen.
  
  
  CONCLUSIONS
  Bosutinib showed promising efficacy in prolonging time to progression in chemotherapy-pretreated patients with locally advanced or metastatic breast cancer. Bosutinib was generally well tolerated, with a safety profile different from that of the Src/Abl tyrosine kinase inhibitor dasatinib in a similar patient population.
authors.affiliation: Department of Medical Oncology, Centre René Gauducheau, Nantes Saint-Herblain; UMR 892 INSERM, Nantes, France. Electronic address: m-campone@nantes.fnclcc.fr.
authors.forename: M
authors.initials: M
authors.lastname: Campone
authors.affiliation: Department of Oncology and Medical Radiology, Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine.
authors.forename: I
authors.initials: I
authors.lastname: Bondarenko
authors.affiliation: Radiotherapy and Oncology Department, Sir Paul Boffa Hospital, Floriana, Malta.
authors.forename: S
authors.initials: S
authors.lastname: Brincat
authors.affiliation: Transcarpathian Regional Clinical Oncology Dispensary, Uzhgorod National University, Uzhgorod, Ukraine.
authors.forename: Y
authors.initials: Y
authors.lastname: Hotko
authors.affiliation: Departments of Breast and Experimental Therapeutics, H. Lee Moffitt Cancer Center, Tampa, USA.
authors.forename: P N
authors.initials: PN
authors.lastname: Munster
authors.affiliation: Multi-Med Salata i Wsp sp. Jawna, Lodz, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Chmielowska
authors.affiliation: Department of Oncology, Centre Georges-François Leclerc, Dijon, France.
authors.forename: P
authors.initials: P
authors.lastname: Fumoleau
authors.affiliation: Department of Medical Oncology, Vincent's Hospital, Darlinghurst, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Ward
authors.affiliation: Pfizer Inc, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Bardy-Bouxin
authors.affiliation: Pfizer Inc, Cambridge, USA.
authors.forename: E
authors.initials: E
authors.lastname: Leip
authors.affiliation: Pfizer Inc, Cambridge, USA.
authors.forename: K
authors.initials: K
authors.lastname: Turnbull
authors.affiliation: Pfizer Inc, Cambridge, USA.
authors.forename: C
authors.initials: C
authors.lastname: Zacharchuk
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong-Kong.
authors.forename: R J
authors.initials: RJ
authors.lastname: Epstein
mesh_terms: D000328:Adult; D000368:Aged; D000814:Aniline Compounds / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009367:Neoplasm Staging; D009570:Nitriles / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011804:Quinolines / Q000627:therapeutic use*; D016879:Salvage Therapy / Q000379:methods*
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011804:Quinolines; C471992:bosutinib; D011505:Protein-Tyrosine Kinases