Neoadjuvant dose-dense gemcitabine plus docetaxel and vinorelbine plus epirubicin for operable breast cancer: improved prognosis in triple-negative tumors

Drugs R D. 2011;11(2):147-57. doi: 10.2165/11591210-000000000-00000.

Abstract

Background: Neoadjuvant anti-tumor activity of an alternating taxane- and anthracycline-based dose-dense regimen in patients with operable, non-inflammatory large breast cancer was investigated.

Objective: The objective is to study the rate of pathological complete response in patients with breast cancer receiving dose-dense chemotherapy sequentially with gemcitabine plus docetaxel and vinorelbine plus epirubicin.

Methods: Women (n = 74) with clinical stage II or III breast cancer were enrolled in this open-label, multicenter study to receive six 2-weekly courses of gemcitabine 1000 mg/m2 plus docetaxel 75 mg/m2 on days 1 and 15, and vinorelbine 25 mg/m2 plus epirubicin 100 mg/m2 on days 29 and 43. Patients with an objective response on day 56 then received another cycle of gemcitabine/docetaxel on day 57 and of vinorelbine/epirubicin on day 71. Conservative surgery was scheduled for all patients.

Results: Of the patients enrolled, 30% had triple-negative breast cancer (TNBC). The pathologic complete response (pCR) rate was 22% overall, but was higher in TNBC than patients without TNBC (40.9% vs 14.0%; p = 0.028). Among patients with a pCR, patients with TNBC had similar recurrence-free survival (RFS) and overall survival (OS) to patients without TNBC. Among those without a pCR, RFS rates for patients with TNBC were significantly lower than for patients without TNBC (p = 0.04). The most common severe hematologic toxicity was neutropenia.

Conclusions: Administering four drugs in a dose-dense alternating sequence gave a high pCR in patients with operable, invasive breast cancer. Patients with TNBC with a pCR had similar OS to patients without TNBC, whereas patients with TNBC without a pCR had poorer survival rate than their non-TNBC counterparts.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Breast Neoplasms / radiotherapy
  • Breast Neoplasms / surgery
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Docetaxel
  • Epirubicin / administration & dosage
  • Epirubicin / therapeutic use*
  • Female
  • Gemcitabine
  • Humans
  • Lymphatic Metastasis / diagnosis
  • Middle Aged
  • Neoadjuvant Therapy / methods*
  • Neoplasm Grading
  • Neoplasm Metastasis / diagnosis
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Prognosis
  • Receptor, ErbB-2 / genetics
  • Receptors, Estrogen / genetics
  • Receptors, Progesterone / genetics
  • Survival Analysis
  • Taxoids / administration & dosage
  • Taxoids / therapeutic use*
  • Treatment Outcome
  • Vinblastine / administration & dosage
  • Vinblastine / analogs & derivatives*
  • Vinblastine / therapeutic use
  • Vinorelbine
  • Young Adult

Substances

  • Receptors, Estrogen
  • Receptors, Progesterone
  • Taxoids
  • Deoxycytidine
  • Docetaxel
  • Epirubicin
  • Vinblastine
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Vinorelbine
  • Gemcitabine