Phase III Randomized Comparison of Adjuvant Therapies in Premenopausal Women with Resected Node-Positive Hormone Receptor-Positive Adenocarcinoma of the Breast: CAF (CTX/DOX/5-FU) vs CAF Followed by ZDX vs CAF Followed by ZDX/TMX
Basic Trial Information
CLB-9192, SWOG-8851, INT-0101, E5188
I. Compare recurrence rates, disease-free intervals, and overall survival of premenopausal women with axillary node-positive, hormone receptor-positive adenocarcinoma of the breast randomly assigned to adjuvant therapy with CAF (cyclophosphamide/doxorubicin/fluorouracil) chemotherapy alone vs. CAF followed by 5 years of goserelin vs. CAF followed by 5 years of goserelin/tamoxifen. II. Compare the toxicities of these 3 regimens. III. Assess the effects of these 3 therapies on LH, FSH, and estradiol levels in these patients.
Histologically proven invasive adenocarcinoma of the breast Tumor excised within previous 12 weeks At least 1 positive lymph node after lower and middle axillary node dissection (6 or more nodes examined) No positive deep mastectomy margins No clinical skin involvement (Focal microscopic dermal involvement and focal microscopic dermal lymphatic involvement acceptable) Hormone receptor status: Estrogen and/or progesterone receptor positive (at least 10 fmol protein/mg by biochemical assay or clearly positive immunocytochemical assay) Primary tumor and nodal disease movable with respect to chest wall No evidence of metastatic disease or contralateral breast cancer, determined by: Preoperative chest x-ray and mammogram (within 3 months prior or 12 weeks after surgery) Appropriate laboratory tests, including negative bone scan None of the following: Peau d'orange skin changes Skin ulceration Inflammatory skin lesions Preoperative edema of the arm Bilateral breast cancer
Biologic therapy: Not specified Chemotherapy: None prior for breast cancer Endocrine therapy: None prior for breast cancer except up to 14 days of tamoxifen Estrogen therapy should be discontinued at diagnosis Radiotherapy: Required on protocol for those with less than total mastectomy May be given to those with total mastectomy Surgery: Excision within previous 12 weeks Lower and middle axillary node dissection (at least 6 nodes) If less than total mastectomy: Tumor 5 cm or less in greatest dimension on mammogram No multiple suspicious calcifications on mammogram Negative inked margins of resection around primary
Age: Not specified Sex: Women only Menopausal status: Premenopausal, defined by one of the following: Within 4 months of LMP 4-12 months since LMP with normal premenopausal FSH level 60 years of age or less with a prior hysterectomy with 1 or both ovaries left intact and normal premenopausal FSH 55 years of age or less and on estrogen therapy for reasons other than surgical castration, with a premenopausal FSH 1-2 weeks after stopping estrogen (If on estrogen therapy following surgical castration prior to diagnosis, patient considered postmenopausal) Performance status: Not specified Hematopoietic: AGC at least 1,500 Platelets at least 100,000 Hepatic: SGOT and alkaline phosphatase no more than 1.2 x normal Negative bone scan required if alkaline phosphatase abnormal Renal: Serum creatinine no more than 1.2 x normal Cardiovascular: No congestive heart failure No angina pectoris No cardiac arrhythmia No myocardial infarction within 12 months No poorly controlled hypertension Pulmonary: No chronic obstructive pulmonary disease (COPD) that limits activity Other: No brittle diabetes No major depression No other medical/neuropsychiatric problems difficult to manage No prior second malignancy within 5 years, except: Curatively treated nonmelanomatous skin cancer Carcinoma in situ of the cervix No pregnancy or lactation Nonhormonal, barrier contraception required during therapy
1,500 patients will be entered over 4 years.
Randomized study. Patients who have had less than total mastectomy receive radiotherapy on Regimen A beginning either prior to initiation of chemotherapy or within 4 weeks after completion of chemotherapy (those who have radiotherapy prior to chemotherapy must complete radiotherapy prior to randomization). The interval between definitive surgery and initiation of adjuvant chemotherapy must not exceed 12 weeks (84 days). Arm I: 3-Drug Combination Chemotherapy. CAF: Cyclophosphamide, CTX, NSC-26271; Doxorubicin, DOX, NSC-123127; Fluorouracil, 5-FU, NSC-19893. Arm II: 3-Drug Combination Chemotherapy followed by Releasing Factor Agonist Therapy. CAF; followed by Goserelin, ZDX, NSC-606864. Arm III: 3-Drug Combination Chemotherapy followed by Releasing Factor Agonist Therapy plus Antiestrogen Therapy. CAF; followed by ZDX; plus Tamoxifen, TMX, NSC-180973. Regimen A: Radiotherapy. Irradiation of breast and supraclavicular and apical axillary nodes (entire axilla in patients with more than 4 positive nodes) using supervoltage equipment followed by a boost to the primary site using Iridium-192 implants or electron beams.
Davidson NE, O'Neill AM, Vukov AM, et al.: Chemoendocrine therapy for premenopausal women with axillary lymph node-positive, steroid hormone receptor-positive breast cancer: results from INT 0101 (E5188). J Clin Oncol 23 (25): 5973-82, 2005.[PUBMED Abstract]
Davidson NE, O'Neill A, Vukov A, et al.: Chemohormonal therapy in premenopausal node-positive, receptor-positive breast cancer: an Eastern Cooperative Oncology Group phase III intergroup trial (E5188,INT-0101). [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-15, 2003.
Davidson N, O'Neill A, Vukov A, et al.: Effect of chemohormonal therapy in premenopausal, node (+), receptor (+) breast cancer: an Eastern Cooperative Oncology Group phase III intergroup trial (E5188, INT-0101). [Abstract] Proceedings of the American Society of Clinical Oncology 18: A-249, 67a, 1999.
Sparano JA, Wang M, Zhao F, et al.: Obesity at diagnosis is associated with inferior outcomes in hormone receptor-positive operable breast cancer. Cancer 118 (23): 5937-46, 2012.[PUBMED Abstract]
Cuzick J, Ambroisine L, Davidson N, et al.: Use of luteinising-hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer: a meta-analysis of individual patient data from randomised adjuvant trials. Lancet 369 (9574): 1711-23, 2007.[PUBMED Abstract]
Trial Contact Information
Trial Lead Organizations
Eastern Cooperative Oncology Group
Southwest Oncology Group
Cancer and Leukemia Group B
Ph: 910-716-7973; 800-446-2255
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.