Phase III Comparison of Adjuvant Chemoendocrine Therapy With CAF and Concurrent or Delayed Tamoxifen to Tamoxifen Alone in Postmenopausal Patients With Involved Axillary Lymph Nodes and Positive Receptors
OBJECTIVES: I. Compare disease-free survival and overall survival of postmenopausal women
with node-positive, estrogen and/or progesterone receptor-positive adenocarcinoma of the
breast randomly assigned to postoperative adjuvant treatment with long-term (5 years)
tamoxifen vs. CAF (cyclophosphamide/doxorubicin/fluorouracil) plus concurrent and long-term
tamoxifen vs. CAF followed by long-term tamoxifen. II. Compare the relative toxicities of
these three regimens.
OUTLINE: Randomized study. All patients are randomized on Arms I, II, and III. Lumpectomy
patients must receive radiotherapy on Regimen A. At the discretion of the physician,
mastectomy patients may receive radiotherapy on Regimen B for a tumor greater than 5 cm in
diameter, 4 or more positive nodes, or extranodal extension of the tumor into the axillary
fat. Patients randomized to Arm I who are to receive radiotherapy should begin as soon as
feasible postoperatively; these patients may be irradiated while receiving tamoxifen.
Patients on Arms II and III who are to receive radiotherapy are treated either
postoperatively prior to registration or after completion of and recovery from 6 courses of
CAF. Arm I: Antiestrogen Therapy. Tamoxifen, TMX, NSC-180973. Arm II: 3-Drug Combination
Chemotherapy followed by Antiestrogen Therapy. CAF: Cyclophosphamide, CTX, NSC-26271;
Doxorubicin, DOX, NSC-123127; Fluorouracil, 5-FU, NSC-19893; followed by TMX. Arm III:
3-Drug Combination Chemotherapy plus Concurrent Antiestrogen Therapy. CAF; plus concurrent
TMX. Regimen A: Radiotherapy. Irradiation of the breast and underlying chest wall and
(optionally) of the supraclavicular area and, if indicated, the axilla, using megavoltage
equipment with photon energies of up to 6 MV followed, if indicated, by a tumor bed boost
using either electrons or iridium-192 (192-Ir) implants. Regimen B: Radiotherapy.
Irradiation of the chest wall using either megavoltage photons via a tangential field or
electrons via a direct field plus (optional) photon irradiation of the supraclavicular area
and, if indicated, the axilla.
PROJECTED ACCRUAL: 350 patients will be randomized to Arm I and 530 patients each will be
randomized to Arms II and III. Accrual should be completed in about 4 years, and 4
additional years will be required for follow-up.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Kathy S. Albain, MD
United States: Federal Government