Phase II study of neoadjuvant docetaxel/ vinorelbine followed by surgery and adjuvant doxorubicin/cyclophosphamide in women with stage II/III breast cancer

Clin Breast Cancer. 2006 Feb;6(6):511-7. doi: 10.3816/CBC.2006.n.004.

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.

Patients and 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.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery*
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Female
  • Humans
  • Infusions, Intravenous
  • Injections, Intravenous
  • Lymphatic Metastasis
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Taxoids / administration & dosage
  • Treatment Outcome
  • Vinblastine / administration & dosage
  • Vinblastine / analogs & derivatives
  • Vinorelbine

Substances

  • Taxoids
  • Docetaxel
  • Vinblastine
  • Doxorubicin
  • Cyclophosphamide
  • Vinorelbine