Docetaxel in Node Positive Adjuvant Breast Cancer (TAX316)

• Number of Participants With Overall Survival Events [ Time Frame: up to 10 year follow-up ] [ Designated as safety issue: No ]
  Overall Survival - time from the date of randomization up to the date of death of any cause.
• Number of Participants With Second Primary Malignancies (Toxicity) [ Time Frame: up to 10 year follow-up ] [ Designated as safety issue: Yes ]
  Toxicity (second primary malignancies)- defined as histopathologically proven cancer, excluding nonmelanomatous skin cancer, in situ carcinoma of the cervix, and in situ carcinoma of the breast.

• Overall survival [ Time Frame: Study period ] [ Designated as safety issue: No ]
• Toxicity and quality of life [ Time Frame: Study period ] [ Designated as safety issue: No ]

The purpose of this study was to compare disease-free survival after treatment with docetaxel in combination with doxorubicin and cyclophosphamide to 5-fluorouracil in combination with doxorubicin and cyclophosphamide in operable breast cancer patients with positive axillary lymph nodes.

In addition to the 5-year analysis conducted in September 2003, two other analyses were planned when 590 and 700 Disease Free Survival events occurred. However, due to the lower than predicted DFS event rate, and in agreement with FDA and EMA, a time-based final analysis at 10 years was considered more appropriate than an event-based (700 Disease Free Survival events) analysis.

• Drug: Docetaxel
  intravenous
  Other Name: Taxotere®
• Drug: 5-fluorouracil
  intravenous
  Other Name: 5-FU
• Drug: Doxorubicin
  intravenous
• Drug: Cyclophosphamide
  intravenous

• Experimental: TAC (Docetaxel)
  docetaxel (75 mg/m^2) in combination with doxorubicin (50 mg/m^2) and cyclophosphamide (500 mg/m^2) on day 1 every 3 weeks for 6 cycles of treatment
  Interventions:

  • Drug: Docetaxel
  • Drug: Doxorubicin
  • Drug: Cyclophosphamide
• Active Comparator: FAC (5-fluorouracil)
  5-fluorouracil (500 mg/m^2) in combination with doxorubicin (50 mg/m^2) and cyclophosphamide (500 mg/m^2) on day 1 every 3 weeks for 6 cycles of treatment
  Interventions:

  • Drug: 5-fluorouracil
  • Drug: Doxorubicin
  • Drug: Cyclophosphamide

• Martin M, Pienkowski T, Mackey J, Pawlicki M, Guastalla JP, Weaver C, Tomiak E, Al-Tweigeri T, Chap L, Juhos E, Guevin R, Howell A, Fornander T, Hainsworth J, Coleman R, Vinholes J, Modiano M, Pinter T, Tang SC, Colwell B, Prady C, Provencher L, Walde D, Rodriguez-Lescure A, Hugh J, Loret C, Rupin M, Blitz S, Jacobs P, Murawsky M, Riva A, Vogel C; Breast Cancer International Research Group 001 Investigators. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005 Jun 2;352(22):2302-13.
• Mackey JR, Martin M, Pienkowski T, Rolski J, Guastalla JP, Sami A, Glaspy J, Juhos E, Wardley A, Fornander T, Hainsworth J, Coleman R, Modiano MR, Vinholes J, Pinter T, Rodríguez-Lescure A, Colwell B, Whitlock P, Provencher L, Laing K, Walde D, Price C, Hugh JC, Childs BH, Bassi K, Lindsay MA, Wilson V, Rupin M, Houé V, Vogel C; TRIO/BCIRG 001 investigators. Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial. Lancet Oncol. 2013 Jan;14(1):72-80. doi: 10.1016/S1470-2045(12)70525-9. Epub 2012 Dec 12.

Inclusion Criteria:

• Histologically proven breast cancer (invasive adenocarcinoma with at least one axillary lymph node showing evidence of tumor among a minimum of six resected lymph nodes).
• Definitive surgical treatment must be either mastectomy, or breast conserving surgery with axillary lymph node dissection for operable breast cancer. Margins of resected specimen from definitive surgery must be histologically free of invasive adenocarcinoma and ductal carcinoma.

Exclusion criteria:

• Prior systemic anticancer therapy for breast cancer (immunotherapy, hormonotherapy, chemotherapy).
• Prior anthracycline therapy or taxoids (paclitaxel, docetaxel) for any malignancy.