title: Phase II study of neoadjuvant docetaxel/ vinorelbine followed by surgery and adjuvant doxorubicin/cyclophosphamide in women with stage II/III breast cancer.
abstract: BACKGROUND
  The purpose of this study was to evaluate the combination of docetaxel plus vinorelbine as neoadjuvant chemotherapy for stage II/III locally advanced breast cancer.
  
  
  METHODS
  Eligible women with stage IIA-IIIB or locoregional stage IV breast cancer were treated before surgery with 6 cycles of docetaxel 60 mg/m2 and vinorelbine 45 mg/m2, repeated every 2 weeks with granulocyte colony-stimulating factor and quinolone prophylaxis. Pathologic complete response (pCR), viewed as an early surrogate for disease-free and overall survival, was the primary efficacy endpoint. Sixty patients were enrolled; 60% had T3 or T4 lesions, 67% had clinically palpable lymph nodes, and 52% were hormone receptor positive.
  
  
  RESULTS
  Fifty-nine patients were evaluable for pathologic response; 16 (27%) exhibited pCR in the breast alone (T0 Tis NX), 20% exhibited a pCR in the breast and lymph nodes (T0 Tis N0), 24 (41%) had < 5 mm of residual tumor, and 28 (47%) had node-negative disease at surgery. Relative dose intensity was 96% for docetaxel and 95% for vinorelbine. The clinical response rate was 98% (59 of 60 patients), including 38 complete responses (63%). Grade 3/4 neutropenia (95%), neutropenic fever (22%), mucositis (5%), and pulmonary toxicity (5%) occurred in >or= 5% of patients. Constipation was seen early but became insignificant after incorporating a prophylactic laxative regimen. Other toxicities have been minimal.
  
  
  CONCLUSIONS
  With a clinical response rate of 98% and an in-breast pCR rate of 27%, docetaxel/vinorelbine is among the most active neoadjuvant regimens reported for locally advanced breast cancer. Docetaxel/vinorelbine can be administered in a dose-dense fashion while maintaining relative dose intensity. However, there was a significant incidence of fever and neutropenia despite the use of prophylactic growth factors and quinolones, indicating that lower doses of docetaxel/vinorelbine should be evaluated in future studies.
authors.affiliation: Carolinas Hematology-Oncology Associates, Charlotte, NC 28203, USA. steven.limentani@carolinashealthcare.org
authors.forename: Steven A
authors.initials: SA
authors.lastname: Limentani
authors.forename: Adam M
authors.initials: AM
authors.lastname: Brufsky
authors.forename: John K
authors.initials: JK
authors.lastname: Erban
authors.forename: Mohammed
authors.initials: M
authors.lastname: Jahanzeb
authors.forename: Deborah
authors.initials: D
authors.lastname: Lewis
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008207:Lymphatic Metastasis; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D014747:Vinblastine; D004317:Doxorubicin; D003520:Cyclophosphamide; D000077235:Vinorelbine