title: Neoadjuvant bevacizumab, docetaxel and capecitabine combination therapy for HER2/neu-negative invasive breast cancer: Efficacy and safety in a phase II pilot study.
abstract: OBJECTIVE
  To evaluate the triplet combination of bevacizumab, capecitabine and docetaxel (XTA) as neoadjuvant therapy for breast cancer.
  
  
  METHODS
  Patients with invasive, HER2-negative, nonmetastatic breast cancer (T2-4c >2cm) and no prior systemic therapy received six 21-day cycles of XTA (bevacizumab 15mg/kg, day 1, cycles 1-5; docetaxel 75mg/m(2), day 1 of each cycle; capecitabine 950mg/m(2) twice daily for 14 days of each cycle). Patients underwent surgery 2-4 weeks after completing XTA, followed by radiotherapy, chemotherapy and hormone therapy according to institution guidelines. Pathologic complete response (pCR), the primary endpoint, was defined as no evidence of invasive tumour in the final surgical sample. Secondary endpoints included rates of clinical response and breast-conserving surgery and safety.
  
  
  RESULTS
  Median age of the 18 enrolled patients was 48 years (range 34-69). Most patients (72%) received six cycles of neoadjuvant therapy. pCR rate was 22% (95% confidence interval [CI]: 6-48). Nine of the patients without pCR achieved clinical partial response, giving a 72% overall clinical response rate (95% CI: 47-90). Fifteen patients underwent breast-conserving surgery (83%; 95% CI: 59-96). One additional patient had breast-conserving surgery, followed by mastectomy 1 month later. The remaining 2 patients underwent modified radical mastectomy. XTA was reasonably well tolerated, with no unexpected toxicities or treatment-related deaths.
  
  
  CONCLUSIONS
  The 22% pCR rate in a HER2-negative population suggests that addition of bevacizumab increases the activity of neoadjuvant capecitabine-docetaxel. Further evaluation of this regimen in early breast cancer is recommended.
authors.affiliation: IIIrd Medical Department with Hematology and Medical Oncology, Private Medical University Hospital Salzburg, Muellner Hauptstrasse 48, Salzburg A-5020, Austria. r.greil@salk.at
authors.forename: R
authors.initials: R
authors.lastname: Greil
authors.forename: M
authors.initials: M
authors.lastname: Moik
authors.forename: R
authors.initials: R
authors.lastname: Reitsamer
authors.forename: S
authors.initials: S
authors.lastname: Ressler
authors.forename: M
authors.initials: M
authors.lastname: Stoll
authors.forename: K
authors.initials: K
authors.lastname: Namberger
authors.forename: C
authors.initials: C
authors.lastname: Menzel
authors.forename: B
authors.initials: B
authors.lastname: Mlineritsch
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077143:Docetaxel; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010865:Pilot Projects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000069287:Capecitabine; D003841:Deoxycytidine; D000077143:Docetaxel; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids