title: A prospective study of concurrent cyclophosphamide/methotrexate/5-fluorouracil and reduced-dose radiotherapy in patients with early-stage breast carcinoma.
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.
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital and the Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA. jbellon@lroc.harvard.edu
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Bellon
authors.forename: Lawrence N
authors.initials: LN
authors.lastname: Shulman
authors.forename: Steven E
authors.initials: SE
authors.lastname: Come
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Li
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Gelman
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Silver
authors.forename: Jay R
authors.initials: JR
authors.lastname: Harris
authors.forename: Abram
authors.initials: A
authors.lastname: Recht
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D011446:Prospective Studies; D011829:Radiation Dosage; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate