title: Metronomic chemotherapy combined with bevacizumab and erlotinib in patients with metastatic HER2-negative breast cancer: clinical and biological activity.
abstract: The aim of this study was to determine the safety and efficacy of metronomic chemotherapy combined with targeted drugs in patients with metastatic breast cancer (MBC). We included 26 untreated patients with HER2-negative (HER-) MBC and poor hormone receptor expression. The analysis of the results suggests that the metronomic chemotherapy combined with bevacizumab and erlotinib is effective and well tolerated.
  
  
  BACKGROUND
  The object of this study was to evaluate the safety and efficacy of metronomic chemotherapy in combination with bevacizumab and erlotinib in patients with HER2-negative (HER2(-)) metastatic breast cancer (MBC) and poor hormone receptor expression.
  
  
  METHODS
  Patients with untreated MBC were candidates to receive metronomic oral capecitabine (500 mg thrice daily) and cyclophosphamide (50 mg daily) plus bevacizumab (15 mg/kg every 3 weeks) and erlotinib (100 mg daily).
  
  
  RESULTS
  Of 24 patients assessable for response, we observed 1 complete response (CR, 4%), 14 partial responses (58%), 5 patients with stable disease greater than 9 weeks' duration (SD, 21%), and 1 patient (4%) with early progression of disease. The overall clinical benefit (CB) (CR + partial response + SD > 24 weeks) was 75% (95% confidence interval [CI], 53%-90%). Median time to progression was 43 weeks (95% CI, 21-69). Patients with low levels of circulating endothelial progenitors (CEPs) at baseline had a significantly improved progression-free survival (PFS). Toxicity was generally mild. Grade 3 toxicity included diarrhea (n = 1), thrombosis (n = 1), and hypertension (n = 2). Grade 2 adverse events included diarrhea (n = 5), hand-foot syndrome (n = 13), and hypertension (n = 4).
  
  
  CONCLUSIONS
  Treatment with metronomic chemotherapy in combination with bevacizumab and erlotinib was effective in HER2(-), estrogen receptor (ER)- and progesterone receptor (PR)-poor advanced breast cancer.
authors.affiliation: Department of Medicine, European Institute of Oncology, Milan, Italy. emilia.montagna@ieo.it
authors.forename: Emilia
authors.initials: E
authors.lastname: Montagna
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cancello
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bagnardi
authors.forename: Davide
authors.initials: D
authors.lastname: Pastrello
authors.forename: Silvia
authors.initials: S
authors.lastname: Dellapasqua
authors.forename: Gino
authors.initials: G
authors.lastname: Perri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.forename: Paolo
authors.initials: P
authors.lastname: Veronesi
authors.forename: Alberto
authors.initials: A
authors.lastname: Luini
authors.forename: Mattia
authors.initials: M
authors.lastname: Intra
authors.forename: Angelica
authors.initials: A
authors.lastname: Calleri
authors.forename: Cristiano
authors.initials: C
authors.lastname: Rampinelli
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertolini
authors.forename: Marco
authors.initials: M
authors.lastname: Colleoni
mesh_terms: D059250:Administration, Metronomic; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068258:Bevacizumab; D054316:Biomarkers, Pharmacological / Q000032:analysis / Q000097:blood / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000069287:Capecitabine; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000473:pathology; D011799:Quinazolines / Q000008:administration & dosage*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D054316:Biomarkers, Pharmacological; D000069287:Capecitabine; D003520:Cyclophosphamide; D003841:Deoxycytidine; D000069347:Erlotinib Hydrochloride; D005472:Fluorouracil; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2; C508053:ERBB2 protein, human