Fifteen-year median follow-up results after neoadjuvant doxorubicin, followed by mastectomy, followed by adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) followed by radiation for stage III breast cancer: a phase II trial (CALGB 8944). Academic Article uri icon

Overview

MeSH

  • Adult
  • Aged
  • Antineoplastic Agents
  • Antineoplastic Combined Chemotherapy Protocols
  • Combined Modality Therapy
  • Cyclophosphamide
  • Disease Progression
  • Doxorubicin
  • Female
  • Fluorouracil
  • Follow-Up Studies
  • Humans
  • Mastectomy
  • Methotrexate
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Radiotherapy, Adjuvant
  • Survival Analysis

MeSH Major

  • Adenocarcinoma
  • Breast Neoplasms

abstract

  • To describe long-term results of a multimodality strategy for stage III breast cancer utilizing neoadjuvant doxorubicin followed by mastectomy, CMF, and radiotherapy. Women with biopsy-proven, clinical stage III breast cancer and adequate organ function were eligible. Neoadjuvant doxorubicin (30 mg/m(2) days 1-3, every 28 days for 4 cycles) was followed by mastectomy, in stable or responding patients. Sixteen weeks of postoperative CMF followed (continuous oral cyclophosphamide (2 mg/kg/day); methotrexate (0.7 mg/kg IV) and fluorouracil (12 mg/kg IV) weekly, weeks 1-8, and than biweekly, weeks 9-16). Radiation therapy followed adjuvant chemotherapy. Clinical response rate was 71% (79/111, 95% CI = 62-79%), with 19% complete clinical response. Pathologic complete response was 5% (95% CI = 2-11%). Median follow-up is 15.6 years. Half of the patients progressed by 2.2 years; half died by 5.4 years (range 6 months-15 years). The hazard of dying was greatest in the first 5 years after diagnosis and declined thereafter. Time to progression and overall survival were predicted by number of pathologically involved lymph nodes (TTP: HR [10 vs. 1 node] 2.40, 95% CI = 1.63-3.53, P < 0.0001; OS: HR 2.50, 95% CI = 1.74-3.58, P < 0.0001). After multimodality treatment for locally advanced breast cancer, long-term survival was correlated with the number of pathologically positive lymph nodes, but not to clinical response. The hazard of death was highest during the first 5 years after diagnosis and declined thereafter, indicating a possible intermediate endpoint for future trials of neoadjuvant treatment.

publication date

  • February 2009

has subject area

  • Adenocarcinoma
  • Adult
  • Aged
  • Antineoplastic Agents
  • Antineoplastic Combined Chemotherapy Protocols
  • Breast Neoplasms
  • Combined Modality Therapy
  • Cyclophosphamide
  • Disease Progression
  • Doxorubicin
  • Female
  • Fluorouracil
  • Follow-Up Studies
  • Humans
  • Mastectomy
  • Methotrexate
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Radiotherapy, Adjuvant
  • Survival Analysis

Research

keywords

  • Clinical Trial, Phase II
  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4217205

Digital Object Identifier (DOI)

  • 10.1007/s10549-008-9943-2

PubMed ID

  • 18306034

Additional Document Info

start page

  • 479

end page

  • 490

volume

  • 113

number

  • 3