title: Postsurgical adjuvant chemotherapy of stage II breast carcinoma with or without crossover to a non-cross-resistant regimen: a Cancer and Leukemia Group B study.
abstract: OBJECTIVE
  To compare two cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP) regimens with a doxorubicin-based regimen--vinblastine, doxorubicin, thiotepa, and Halotestin (Upjohn, Kalamazoo, MI) (VATH)--in patients with stage II node-positive breast carcinoma.
  
  
  METHODS
  Nine hundred forty-five women were treated with a 6-week induction course of CMFVP. They were then randomized to receive one of two consolidation CMFVP regimens: 6-week courses or 2-week courses. Following completion of CMFVP consolidation, patients were again randomized to either continue the CMFVP regimen or to receive six escalating doses of VATH.
  
  
  RESULTS
  Among all patients, with a median follow-up time of 11.5 years, there is no statistically significant difference in disease-free survival (DFS) between the two consolidation CMFVP regimens. VATH intensification treatment is statistically significantly superior to CMFVP in terms of DFS (P = .0040). For patients with one to three involved nodes, there is currently no significant difference between VATH and CMFVP; however, among those with four or more positive lymph nodes, there is a significant difference in favor of VATH (P = .0037). There is also improved overall survival with VATH (P = .043; median, > 14 years v 10 years). This difference is also statistically significant in patients with four or more involved lymph nodes, among postmenopausal patients, and among postmenopausal estrogen receptor-positive patients.
  
  
  CONCLUSIONS
  Chemotherapy with crossover to escalating doses of VATH following CMFVP was well tolerated and effective. Inauguration of VATH as a treatment intensification at the eighth month produced a major increase in relapse-free and overall survival. The observation that sensitivity to VATH is retained so long after mastectomy raises questions about the proper duration of adjuvant chemotherapy and lends support to further investigation of cross-over designs in future trials to postoperative adjuvant chemotherapy regimens.
authors.affiliation: National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7329, USA.
authors.forename: M
authors.initials: M
authors.lastname: Perloff
authors.forename: L
authors.initials: L
authors.lastname: Norton
authors.forename: A H
authors.initials: AH
authors.lastname: Korzun
authors.forename: W C
authors.initials: WC
authors.lastname: Wood
authors.forename: R W
authors.initials: RW
authors.lastname: Carey
authors.forename: A
authors.initials: A
authors.lastname: Gottlieb
authors.forename: J C
authors.initials: JC
authors.lastname: Aust
authors.forename: A
authors.initials: A
authors.lastname: Bank
authors.forename: R T
authors.initials: RT
authors.lastname: Silver
authors.forename: F
authors.initials: F
authors.lastname: Saleh
authors.forename: G P
authors.initials: GP
authors.lastname: Canellos
authors.forename: M C
authors.initials: MC
authors.lastname: Perry
authors.forename: R B
authors.initials: RB
authors.lastname: Weiss
authors.forename: J F
authors.initials: JF
authors.lastname: Holland
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005474:Fluoxymesterone / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011184:Postoperative Period; D011241:Prednisone / Q000008:administration & dosage; D011336:Probability; D016019:Survival Analysis; D013852:Thiotepa / Q000008:administration & dosage; D014747:Vinblastine / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D014747:Vinblastine; D004317:Doxorubicin; D003520:Cyclophosphamide; D013852:Thiotepa; D005474:Fluoxymesterone; D005472:Fluorouracil; D011241:Prednisone; D008727:Methotrexate