Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information

Basic Trial Information

Objectives

I.  Test the concept that introduction of the noncross-resistant 
adriamycin-containing regimen TsAVbth in an alternating sequence with CMF(P)TH 
will be superior to CMFPT alone.
II.  Test the theoretical advantage of providing exposure to an antiestrogen 
for prolonged periods against discontinuing its use with the termination of 
chemotherapy.
III.  Compare these effects with respect to decreasing the recurrence rate 
across time, increasing survival across time, and impact of pretreatment 
characteristics on the above parameters.
IV.  Assess the quality of survival from performance status and toxicity 
analysis of the regimens.
V.  Assess the effectiveness of indefinite tamoxifen therapy beyond five years 
of its induction vs. discontinuation of the drug at five years in patients who 
are disease free after chemohormonal therapy (objective added per Addendum 7, 
March 1986).

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Premenopausal female patients who 
have had a total mastectomy and either axillary dissection or low axillary 
sampling (within 6 weeks of study entry) for potentially curable breast 
carcinoma, and who have one or more histologically proven positive axillary 
nodes.  Primary ER tumor and nodal status must be known.  The tumor must be 
less than or equal to 5 cm (pathologically) and be confined to the breast or 
breast and the ipsilateral axilla; it must be movable in relation to the skin, 
underlying muscle, or chest wall.  Axillary nodes must be movable in relation 
to the chest wall and neurovascular bundle.  There must be no preoperative 
edema of the arm and no metastasis other than ipsilateral axillary nodes.  
Patients with inflammatory carcinoma, bilateral malignancy, or any form of 
prior therapy for breast carcinoma are ineligible.  There must have been no 
prior therapy for the current disease; a biopsy performed more than 4 weeks 
prior to total mastectomy will render a patient ineligible.  Previous or 
concomitant malignancy (except squamous or basal cell carcinoma of the skin or 
effectively treated in situ carcinoma of the cervix) is not permitted.  
Patients must have normal FBS and normal hematologic, renal, and hepatic 
function.  Bone scan must show no abnormalities resulting from the malignancy. 
 Pregnant patients are ineligible.  Patients with nonmalignant systemic 
disease (e.g., cardiovascular, renal, hepatic) or other disorders (e.g., 
diabetes mellitus requiring insulin or oral hypoglycemic drugs, active peptic 
ulcer disease, congestive heart failure) that would preclude their being 
subject to any of the treatment options are ineligible, as are those with any 
psychiatric disorder that would preclude informed consent.  Patients must not 
be under treatment for high blood pressure with drugs other than diuretics 
(per Addendum 10, February 1987, all patients must have a diastolic blood 
pressure of no greater than 90).  Per Addendum 3, July 1983, patients with 
clinically non-inflammatory breast cancer who have dermal invasion not 
involving the lymphatics are eligible; involvement of the lymphatics excludes.

Expected Enrollment

438 female patients is the accrual goal.  Per Addendum 6, September 1985, the 
accrual goal for this study has been raised to 625 patients.  Per Addendum 7, 
March 1986, 108 patients are expected to be eligible for the third 
randomization to continue TMX indefinitely vs. observation, with accrual 
requiring 6 years.

Outline

Randomized study.  Patients are randomized between Arms I and II, after which 
all patients are rerandomized to Arm III or IV.  Per Addendum 7, March 1986, 
patients randomized to Arm III who complete 5 years of tamoxifen therapy and 
remain disease free are eligible for a third randomization to receive 
indefinite treatment with tamoxifen or to discontinue tamoxifen.
Arm I:  4-Drug Combination Chemotherapy plus Hormonal Therapy.  CMFPT:  
Cyclophosphamide, CTX, NSC-26271; Methotrexate, MTX, NSC-740; 5-Fluorouracil, 
5-FU, NSC-19893; Prednisone, PRED, NSC-10023; plus Tamoxifen, TMX, NSC-180973.
Arm II:  Alternating 4-Drug and 3-Drug Combination Chemotherapies plus 
Hormonal Therapy.  CMF(P)TH:  CMFPT; plus Halotestin, FXM, NSC-12165; 
alternating with TsAVbTH:  Thiotepa, NSC-6396; Adriamycin, ADR, NSC-123127; 
Vinblastine, VBL, NSC-49842; plus TMX; FXM.
Arm III:  Single-agent Hormonal Therapy.  TMX.
Arm IV:  Observation.

Tormey DC, Gray R, Abeloff MD, et al.: Adjuvant therapy with a doxorubicin regimen and long-term tamoxifen in premenopausal breast cancer patients: an Eastern Cooperative Oncology Group trial. J Clin Oncol 10 (12): 1848-56, 1992.[PUBMED Abstract]

Recht A, Gray R, Davidson NE, et al.: Locoregional failure 10 years after mastectomy and adjuvant chemotherapy with or without tamoxifen without irradiation: experience of the Eastern Cooperative Oncology Group. J Clin Oncol 17 (6): 1689-700, 1999.[PUBMED Abstract]

Tormey DC, Gray R, Falkson HC: Postchemotherapy adjuvant tamoxifen therapy beyond five years in patients with lymph node-positive breast cancer. Eastern Cooperative Oncology Group. J Natl Cancer Inst 88 (24): 1828-33, 1996.[PUBMED Abstract]

Tallman MS, Gray R, Bennett JM, et al.: Leukemogenic potential of adjuvant chemotherapy for early-stage breast cancer: the Eastern Cooperative Oncology Group experience. J Clin Oncol 13 (7): 1557-63, 1995.[PUBMED Abstract]

Saphner T, Tormey DC, Gray R: Venous and arterial thrombosis in patients who received adjuvant therapy for breast cancer. J Clin Oncol 9 (2): 286-94, 1991.[PUBMED Abstract]

Tormey DC, Gray R, Harrington DP: Preliminary ECOG analysis of treatment failure in primary operable breast cancer patients. Oncology (Williston Park) 5 (6): 138-9, 1991.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Douglass Tormey, MD, PhD, Protocol chair		Ph: 303-320-2121

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