title: Adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil, vincristine, and prednisone compared with single-agent L-phenylalanine mustard for patients with operable breast carcinoma and positive axillary lymph nodes: 20-year results of a Southwest Oncology Group study.
abstract: BACKGROUND
  Adjuvant combination chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil plus vincristine and prednisone (CMFVP) was compared with single-agent L-phenylalanine mustard (L-PAM) for the treatment of patients with axillary lymph node positive primary breast carcinoma over 20-years of follow-up.
  
  
  METHODS
  Four hundred forty-one women with axillary lymph node positive breast carcinoma were randomized to receive either combination chemotherapy with cyclophosphamide (60 mg/m(2) orally every day for 1 year), fluorouracil (300 mg/m(2) intravenously [IV] weekly for 1 year), methotrexate (15 mg/m(2) IV weekly for 1 year), vincristine (0.625 mg/m(2) IV for 10 weeks), prednisone (30 mg/m(2) orally on Days 1-14, 20 mg/m(2) on Days 15-28, and 10 mg/m(2) on Days 29-42), or single-agent chemotherapy with L-PAM (5 mg/m(2) orally every day for 5 days every 6 weeks for 2 years) after undergoing surgery. Patients were stratified according to menopausal status and number of positive lymph nodes (1-3 positive lymph nodes or > 3 positive lymph nodes). Seventy-seven patients were ineligible.
  
  
  RESULTS
  The maximum follow-up is 24 years, with a median follow-up of 21.5 years. Disease free survival and overall survival were superior with CMFVP (two-sided log-rank test; P = 0.0008 and P = 0.007, respectively). For all patients, the estimated 20-year survival rate of patients who received CMFVP was 40% compared with 27% for patients who received L-PAM. There was a substantial survival benefit for CMFVP compared with L-PAM in the subsets of premenopausal patients and patients with four or more positive lymph nodes. The estimated 20-year survival rate for premenopausal women who received CMFVP was 49% compared with 33% for premenopausal women who received L-PAM. Among women with > or = 4 positive lymph nodes, the estimated survival rate for patients who received CMFVP was 31% compared with 15% for patients who received L-PAM. Both regimens were tolerated well. Toxicity was more severe and frequent among patients who received CMFVP.
  
  
  CONCLUSIONS
  The authors conclude that, after 20 years of follow-up, adjuvant chemotherapy with CMFVP remains superior to L-PAM for the treatment of patients with lymph node positive breast carcinoma.
authors.affiliation: Swedish Cancer Institute, Seattle, Washington, USA.
authors.forename: Saul E
authors.initials: SE
authors.lastname: Rivkin
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Green
authors.forename: Danika
authors.initials: D
authors.lastname: Lew
authors.forename: John J
authors.initials: JJ
authors.lastname: Costanzi
authors.forename: John W
authors.initials: JW
authors.lastname: Athens
authors.forename: C Kent
authors.initials: CK
authors.lastname: Osborne
authors.forename: Clarence B
authors.initials: CB
authors.lastname: Vaughn
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001365:Axilla; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008207:Lymphatic Metastasis; D015411:Mastectomy, Modified Radical; D015409:Mastectomy, Radical; D008558:Melphalan / Q000009:adverse effects / Q000627:therapeutic use*; D008593:Menopause; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D014750:Vincristine; D003520:Cyclophosphamide; D008558:Melphalan; D005472:Fluorouracil; D011241:Prednisone; D008727:Methotrexate