Phase III Adjuvant Therapy with CMFPT vs CMF(P)TH and TsAVbTH, Followed by TMX vs Observation for Resected Premenopausal Breast Cancer
Basic Trial Information
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).
See General Eligibility Criteria
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.
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.
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
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.