title: Metronomic cyclophosphamide and capecitabine combined with bevacizumab in advanced breast cancer.
abstract: OBJECTIVE
  Metronomic chemotherapy has shown efficacy in patients with metastatic breast cancer. When used in association with targeted antiangiogenic drugs, it was more active than metronomic therapy alone in preclinical and clinical studies.
  
  
  METHODS
  Patients with advanced breast cancer were candidates to receive metronomic oral capecitabine (500 mg thrice daily) and cyclophosphamide (50 mg daily) plus bevacizumab (10 mg/kg every 2 weeks).
  
  
  RESULTS
  In 46 assessable patients, we observed one complete response (CR; 2%), 21 partial responses (PR; 46%), 19 patients (41%) with stable disease (SD), and five patients (11%) with progressive disease, for an overall response rate of 48% (95% CI, 33% to 63%). Additional long-term disease stabilization (SD > or = 24 weeks) occurred in eight patients, for an overall clinical benefit (CR + PR + SD > or = 24 weeks) of 68% (95% CI, 51% to 81%). Median time to progression was 42 weeks (95% CI, 26 to 72 weeks). Toxicity was generally mild. Grade 3 or 4 nonhematologic adverse effects included hypertension (n = 8), transaminitis (n = 2), and nausea/vomiting (n = 2). Higher baseline circulating endothelial cells (CECs) were correlated with overall response (P = .02), clinical benefit (P = .01), and improved progression-free survival (P = .04).
  
  
  CONCLUSIONS
  Treatment with metronomic capecitabine and cyclophosphamide in combination with bevacizumab was effective in advanced breast cancer and was minimally toxic. The number of baseline CECs significantly correlated with response and outcome, therefore supporting further studies on this surrogate marker for the selection of patients to be candidates for antiangiogenic treatments.
authors.affiliation: Medical Senology Research Unit and Division of Medical Oncology, Department of Medicine, European Institute of Oncology, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Dellapasqua
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertolini
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bagnardi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Campagnoli
authors.forename: Eloise
authors.initials: E
authors.lastname: Scarano
authors.forename: Rosalba
authors.initials: R
authors.lastname: Torrisi
authors.forename: Yuval
authors.initials: Y
authors.lastname: Shaked
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mancuso
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: Andrea
authors.initials: A
authors.lastname: Rocca
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pietri
authors.forename: Marco
authors.initials: M
authors.lastname: Colleoni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy*; D000069287:Capecitabine; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D003520:Cyclophosphamide; D005472:Fluorouracil