A prospective study of concurrent cyclophosphamide/methotrexate/5-fluorouracil and reduced-dose radiotherapy in patients with early-stage breast carcinoma

Cancer. 2004 Apr 1;100(7):1358-64. doi: 10.1002/cncr.20136.

Abstract

Background: Concurrent administration of chemotherapy and radiotherapy has the potential advantage of delaying neither treatment and providing radiation sensitization. However, the optimal approach to concurrent treatment in women with early-stage breast carcinoma remains undefined. We present updated results of a prospective protocol of concurrent cyclophosphamide/methotrexate/5-fluorouracil (CMF) and reduced-dose radiotherapy, focusing on tumor control and patient tolerance.

Methods: One hundred twelve women with AJCC Stage I or Stage II breast carcinoma with 0-3 positive axillary lymph nodes were enrolled in a prospective single-arm study of concurrent CMF and reduced-dose radiotherapy (39.6 gray [Gy] to the whole breast, 16-Gy boost). A high proportion of women had risk factors associated with an increased risk of local disease recurrence, including age <40 (32%), close or positive margins (37%), or lymphatic/vascular invasion (51%). The median follow-up period was 94 months.

Results: The 5-year overall survival rate was 94%. By 60 months, 5 patients (4%) experienced local disease recurrence and 19 patients (17%) experienced distant metastasis. There were no isolated regional lymph node recurrences. Local disease recurrence occurred in 1 of 25 patients (4%), 1 of 16 patients (6%), and 3 of 70 patients (4%) with positive, close (<1 mm), and negative margins, respectively. One patient developed acute myelogenous leukemia. An additional patient developed Grade 2 pneumonitis. Cosmetic results were not recorded uniformly for all patients and therefore could not be reliably analyzed.

Conclusions: Concurrent CMF and reduced-dose radiotherapy resulted in a low level of late toxicity and excellent local tumor control, despite the large proportion of patients with substantial risk factors for local disease recurrence. Future studies of concurrent regimens, particularly in patients at high risk of local disease recurrence, are warranted.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / radiotherapy*
  • Breast Neoplasms / surgery
  • Combined Modality Therapy
  • Cyclophosphamide / therapeutic use*
  • Female
  • Fluorouracil / therapeutic use*
  • Humans
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology
  • Prospective Studies
  • Radiation Dosage
  • Risk Factors
  • Survival Analysis
  • Treatment Outcome

Substances

  • Cyclophosphamide
  • Fluorouracil
  • Methotrexate

Supplementary concepts

  • CMF regimen