title: Concurrent bevacizumab with a sequential regimen of doxorubicin and cyclophosphamide followed by docetaxel and capecitabine as neoadjuvant therapy for HER2- locally advanced breast cancer: a phase II trial of the NSABP Foundation Research Group.
abstract: BACKGROUND
  Bevacizumab with chemotherapy improves outcomes in patients with metastatic breast cancer (MBC). The purpose of this trial was to determine the activity and safety profile of neoadjuvant bevacizumab with chemotherapy in women with locally advanced breast cancer (LABC).
  
  
  METHODS
  Between November 2006 and August 2007, 45 women with HER2(-) LABC began preoperative standard AC (doxorubicin [Adriamycin], cyclophosphamide) × 4 cycles followed by docetaxel 75 mg/m(2) intravenously (I.V.) on day 1 and capecitabine 825 mg/m(2) twice daily on days 1-14 (TX, docetaxel [Taxotere] and capecitabine [Xeloda]) every 21 days for 4 cycles. Bevacizumab 15 mg/kg I.V. was given concurrently with chemotherapy every 21 days for a total of 6 preoperative doses. Postoperatively bevacizumab was resumed for a total of 10 doses. The primary endpoint was pathologic complete response (pCR) in the breast.
  
  
  RESULTS
  Thirty patients (66.7%) had stage IIIA disease, 12 (26.7%) patients had stage IIIB, and 3 patients (6.7%) had stage IIIC. Of these, 10 (22%) had inflammatory breast cancer (IBC), and 27 (60%) had estrogen receptor (ER)(+) disease. A pCR in the breast with negative axillary nodes was documented in 4 (9%) of 45 patients. Toxicities that were seen with AC and bevacizumab included fatigue (grade 2/3; 31% and 9%, respectively), mucositis (grade 2/3; 29% and 2%, respectively), and headache (grade 2/3; 16% and 7%, respectively). Toxicities seen with TX and bevacizumab included mucositis (grade 2/3; 48% and 25%, respectively), fatigue (grade 2/3; 43% and 18%, respectively), and hand-foot syndrome (grade 2/3; 34% and 23%, respectively).
  
  
  CONCLUSIONS
  This regimen demonstrated only modest activity with substantial toxicity and does not appear to warrant further evaluation.
authors.affiliation: National Surgical Adjuvant Breast and Bowel Project, Four Allegheny Center, Pittsburgh, PA 15212, USA. rastogip@upmc.edu
authors.forename: Priya
authors.initials: P
authors.lastname: Rastogi
authors.forename: Marc E
authors.initials: ME
authors.lastname: Buyse
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Swain
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Jacobs
authors.forename: André
authors.initials: A
authors.lastname: Robidoux
authors.forename: Marcia K
authors.initials: MK
authors.lastname: Liepman
authors.forename: Eduardo R
authors.initials: ER
authors.lastname: Pajon
authors.forename: Philip A
authors.initials: PA
authors.lastname: Dy
authors.forename: Juan G
authors.initials: JG
authors.lastname: Posada
authors.forename: Marianne K
authors.initials: MK
authors.lastname: Melnik
authors.forename: Fanny
authors.initials: F
authors.lastname: Piette
authors.forename: Charles E
authors.initials: CE
authors.lastname: Geyer
authors.forename: Elfetherios P
authors.initials: EP
authors.lastname: Mamounas
authors.forename: Norman
authors.initials: N
authors.lastname: Wolmark
mesh_terms: 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* / Q000473:pathology; D000069287:Capecitabine; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000069287:Capecitabine; D003520:Cyclophosphamide; D003841:Deoxycytidine; D000077143:Docetaxel; D004317:Doxorubicin; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D043823:Taxoids