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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

Phase 3
18 Years
Not Enrolling
Breast Cancer

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Trial Information

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.

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically proven adenocarcinoma of the breast No apocrine,
adenoidcystic, or squamous carcinomas or sarcomas Pathologic Stage T1-3a, pathologic N1-2
(clinical N0-1), M0: Rendered free of gross tumor at surgery Primary tumor movable with
respect to chest wall Axillary nodes movable with respect to chest wall and each other No
preoperative edema of the arm, peau d'orange, skin ulceration, or inflammatory lesions One
or more positive lymph nodes required No positive deep mastectomy margins or clinical skin
involvement (focal microscopic dermal invasion or focal microscopic dermal lymphatic
involvement allowed) No evidence of metastatic disease on pretherapy studies (including
chest x-ray, bone scan, and mammogram) No bilateral invasive tumors Patients who had
noninvasive ductal carcinoma in situ of the opposite breast and underwent prophylactic
contralateral mastectomy are eligible Hormone receptor status: Positive for estrogen
and/or progesterone receptors (at least 10 fmol/mg protein or unequivocally positive
immunocytochemical assay for one or both) Participation in SWOG-8854 (flow cytometry)

PATIENT CHARACTERISTICS: Age: Any age Sex: Females only Menopausal status: Postmenopausal
as defined by 1 or more of the following: Bilateral oophorectomy at least 2 months prior
to diagnosis of breast cancer (with or without estrogen therapy following surgery) Prior
hysterectomy with at least 1 ovary remaining and either over 60 years old or with a
postmenopausal FSH level Natural menopause (last menstrual period at least 1 year prior to
registration or 4-12 months prior to registration with a postmenopausal FSH level) Treated
with postmenopausal estrogen therapy and either over 55 years old or with a postmenopausal
FSH level Performance status: Not specified Hematopoietic: WBC at least 3,500/mm3 Platelet
count at least 100,000/mm3 Hepatic: Bilirubin no more than 1.2 x normal Alkaline
phosphatase no more than 1.2 x normal SGOT or SGPT no more than 1.2 x normal Renal:
Creatinine no more than 2.0 mg/dL Cardiovascular: No uncontrolled hypertension No history
of ischemic heart disease or CHF Normal ejection fraction by MUGA (required only if deemed
clinically necessary for assessment) Other: No medical condition that would preclude
protocol therapy: No severe diabetes No active ulcer disease No significant psychiatric
disease No second malignancy within 5 years except: Adequately treated nonmelanomatous
skin cancer Curatively treated Stage I cervical carcinoma Pretreatment mammogram and chest
x-ray completed no more than 3 months preoperatively; blood/body fluid analyses to
determine eligibility completed within 14 days prior to registration; prestudy bone scan
completed within 12 weeks prior to registration and/or within 4 weeks prior to surgery

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior
chemotherapy Endocrine therapy: No prior hormonal therapy (except for up to 14 days of
tamoxifen stopped prior to registration) Prior estrogen- and/or progesterone-containing
hormone preparations for nononcologic therapy allowed, but must be discontinued prior to
registration Postmenopausal estrogen therapy should be discontinued in all patients at the
time of diagnosis of breast cancer Radiotherapy: Postoperative chest wall and/or regional
lymph node irradiation allowed for mastectomy patients (at discretion of the physician)
either prior to registration or on protocol for any of the following: Tumor greater than 5
cm in diameter 4 or more positive nodes Extranodal extension of tumor into the axillary
fat No radiotherapy for any other reason in mastectomy patients Postoperative radiotherapy
either prior to registration, during tamoxifen, or after completion of chemotherapy
required for lumpectomy patients Radiotherapy must be completed (if it is to be given
before chemotherapy) prior to registration No immediate radiotherapy after randomization
to chemotherapy Surgery: Radical, modified radical, or breast-sparing surgical procedure
with at least a level I and II axillary dissection and analysis of at least 6 nodes
required within 12 weeks prior to registration Lumpectomy must include: Total excisional
biopsy with rim of normal breast tissue Microscopically negative margins Level I and II
axillary dissection Tumor no more than 5 cm in greatest diameter Clinical and mammographic
examination demonstrating absence of multicentric lesions Type of surgery, number of nodes
examined, number of positive nodes, and size of the primary tumor (size of the largest
tumor if more than 1 mass) must be recorded

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Disease-free survival

Outcome Time Frame:

eight years

Safety Issue:


Principal Investigator

Kathy S. Albain, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Loyola University


United States: Federal Government

Study ID:




Start Date:

May 1989

Completion Date:

March 2010

Related Keywords:

  • Breast Cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • Breast Neoplasms