title: Phase II study of gemcitabine and bevacizumab as first-line treatment in taxane-pretreated, HER2-negative, locally recurrent or metastatic breast cancer.
abstract: BACKGROUND
  In first-line treatment of metastatic breast cancer, the best use of the available therapeutic agents is unclear. This study evaluated the efficacy and safety of combined therapy with bevacizumab and gemcitabine.
  
  
  METHODS
  Women who were to undergo first-line treatment for locoregionally recurrent or metastatic breast cancer were eligible. Patients must have received a taxane-containing regimen in the neoadjuvant and/or adjuvant setting with a ≥ 12-month disease-free interval.
  
  
  METHODS
  This was a single-arm, phase II trial. On day 1 of each 14-day cycle, patients received gemcitabine (2500 mg/m(2)) followed by bevacizumab (10 mg/kg). Patients were treated until complete response, progressive disease (PD), or intolerable toxicity. The primary endpoint was progression-free survival (PFS).
  
  
  RESULTS
  Fifty-two women were enrolled and treated. The median PFS was 4.8 months (95% confidence interval [CI], 3.4-7.6), the 1-year overall survival rate was 68.7% (95% CI, 54.1%-79.5%), and the response rate was 21.4% (95% CI, 10.3%-36.8%). The clinical benefit rate was 35.7%. The median PFS in the triple-negative (n = 19) and non-triple-negative (n = 33) subsets was 3.9 months (95% CI, 2.7-11.7) and 4.9 months (95% CI, 3.4-8.1), respectively. The most common (all grades) drug-related adverse events (AEs) were nausea (51.9%), fatigue (46.2%), decreased appetite (25.0%), and anemia (25.0%). The most common grade 3 or grade 4 drug-related AEs were neutropenia (13.5%), leukopenia (11.5%), and hypertension (7.7%).
  
  
  CONCLUSIONS
  Although the gemcitabine-bevacizumab doublet appears active, the median PFS was lower than expected. There were no unexpected safety signals at this dose and schedule of this combination.
authors.affiliation: Mercy Clinic, St. Louis Cancer and Breast Institute, St. Louis, MO, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Borson
authors.forename: Graydon
authors.initials: G
authors.lastname: Harker
authors.forename: James
authors.initials: J
authors.lastname: Reeves
authors.forename: Thaddeus
authors.initials: T
authors.lastname: Beck
authors.forename: Steven
authors.initials: S
authors.lastname: Hager
authors.forename: William
authors.initials: W
authors.lastname: Horvath
authors.forename: Michael
authors.initials: M
authors.lastname: Jones
authors.forename: Guy
authors.initials: G
authors.lastname: Tillinghast
authors.forename: Edward
authors.initials: E
authors.lastname: Arrowsmith
authors.forename: Grant
authors.initials: G
authors.lastname: Harrer
authors.forename: Fred J
authors.initials: FJ
authors.lastname: Kudrik
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Malamud
authors.forename: Jane
authors.initials: J
authors.lastname: Bromund
authors.forename: Haoyue
authors.initials: H
authors.lastname: Zeigler
authors.forename: Datchen Fritz
authors.initials: DF
authors.lastname: Tai
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Kornberg
authors.forename: Coleman
authors.initials: C
authors.lastname: Obasaju
authors.forename: Mauro
authors.initials: M
authors.lastname: Orlando
authors.forename: Denise A
authors.initials: DA
authors.lastname: Yardley
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D001952:Bridged-Ring Compounds; D003841:Deoxycytidine; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000093542:Gemcitabine; C080625:taxane