title: Bevacizumab added to neoadjuvant chemotherapy for breast cancer.
abstract: BACKGROUND
  Bevacizumab and the antimetabolites capecitabine and gemcitabine have been shown to improve outcomes when added to taxanes in patients with metastatic breast cancer. The primary aims of this trial were to determine whether the addition of capecitabine or gemcitabine to neoadjuvant chemotherapy with docetaxel, followed by doxorubicin plus cyclophosphamide, would increase the rates of pathological complete response in the breast in women with operable, human epidermal growth factor receptor 2 (HER2)-negative breast cancer and whether adding bevacizumab to these chemotherapy regimens would increase the rates of pathological complete response.
  
  
  METHODS
  We randomly assigned 1206 patients to receive neoadjuvant therapy consisting of docetaxel (100 mg per square meter of body-surface area on day 1), docetaxel (75 mg per square meter on day 1) plus capecitabine (825 mg per square meter twice a day on days 1 to 14), or docetaxel (75 mg per square meter on day 1) plus gemcitabine (1000 mg per square meter on days 1 and 8) for four cycles, with all regimens followed by treatment with doxorubicin-cyclophosphamide for four cycles. Patients were also randomly assigned to receive or not to receive bevacizumab (15 mg per kilogram of body weight) for the first six cycles of chemotherapy.
  
  
  RESULTS
  The addition of capecitabine or gemcitabine to docetaxel therapy, as compared with docetaxel therapy alone, did not significantly increase the rate of pathological complete response (29.7% and 31.8%, respectively, vs. 32.7%; P=0.69). Both capecitabine and gemcitabine were associated with increased toxic effects--specifically, the hand-foot syndrome, mucositis, and neutropenia. The addition of bevacizumab significantly increased the rate of pathological complete response (28.2% without bevacizumab vs. 34.5% with bevacizumab, P=0.02). The effect of bevacizumab on the rate of pathological complete response was not the same in the hormone-receptor-positive and hormone-receptor-negative subgroups. The addition of bevacizumab increased the rates of hypertension, left ventricular systolic dysfunction, the hand-foot syndrome, and mucositis.
  
  
  CONCLUSIONS
  The addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response, which was the primary end point of this study. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00408408.).
authors.affiliation: Medical College of Virginia School of Medicine and the Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298-0011, USA. hdbear@vcu.edu
authors.forename: Harry D
authors.initials: HD
authors.lastname: Bear
authors.forename: Gong
authors.initials: G
authors.lastname: Tang
authors.forename: Priya
authors.initials: P
authors.lastname: Rastogi
authors.forename: Charles E
authors.initials: CE
authors.lastname: Geyer
authors.forename: André
authors.initials: A
authors.lastname: Robidoux
authors.forename: James N
authors.initials: JN
authors.lastname: Atkins
authors.forename: Luis
authors.initials: L
authors.lastname: Baez-Diaz
authors.forename: Adam M
authors.initials: AM
authors.lastname: Brufsky
authors.forename: Rita S
authors.initials: RS
authors.lastname: Mehta
authors.forename: Louis
authors.initials: L
authors.lastname: Fehrenbacher
authors.forename: James A
authors.initials: JA
authors.lastname: Young
authors.forename: Francis M
authors.initials: FM
authors.lastname: Senecal
authors.forename: Rakesh
authors.initials: R
authors.lastname: Gaur
authors.forename: Richard G
authors.initials: RG
authors.lastname: Margolese
authors.forename: Paul T
authors.initials: PT
authors.lastname: Adams
authors.forename: Howard M
authors.initials: HM
authors.lastname: Gross
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Costantino
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Swain
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Mamounas
authors.forename: Norman
authors.initials: N
authors.lastname: Wolmark
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D000069287:Capecitabine; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D016015:Logistic Models; D015412:Mastectomy, Segmental; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000069287:Capecitabine; D003520:Cyclophosphamide; D003841:Deoxycytidine; D000077143:Docetaxel; D004317:Doxorubicin; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000093542:Gemcitabine