Phase III Randomized Study of Adjuvant Anthracycline and Cyclophosphamide and Cyclophosphamide, Methotrexate, and Fluorouracil with vs without a 16-Week Treatment Free Interval Between Regimens and with vs without Subsequent Tamoxifen in Premenopausal Women with Node Positive Breast Cancer Unsuitable for Endocrine Therapy Alone
Combination Chemotherapy With or Without Hormone Therapy in Treating Premenopausal Women With Node-Positive Breast Cancer
Basic Trial Information
I. Evaluate the importance of a 16-week gap vs. no treatment gap between two sequential adjuvant chemotherapy regimens (4 courses anthracycline and cyclophosphamide followed by 3 courses of cyclophosphamide, methotrexate, and fluorouracil) on overall survival and local and systemic disease free survival in premenopausal women with node positive breast cancer who are considered unsuitable for endocrine therapy alone. II. Evaluate these same endpoints in patients randomized to either schedule with vs without tamoxifen maintenance therapy. III. Compare the quality of life of patients treated on these regimens. IV. Compare the toxic effects of these regimens.
Histologically proven stage T1-3, pN1, M0 carcinoma of the breast considered unsuitable for adjuvant treatment with endocrine therapy alone Potentially curative resection within 6 weeks of entry by one of the following: Total mastectomy with negative margins Breast-conserving procedure (lumpectomy or quadrantectomy) for tumors less than 5 cm Adequate re-resection or mastectomy within 4 weeks of initial surgery required if margins are positive after initial surgery Axillary clearance (not sampling) required at surgery, with at least 1 node positive upon histopathologic examination of at least 8 nodes Suspicious manifestations of metastatic disease (e.g., hot spots on bone scan, skeletal pain of unknown cause) must be proven benign No bilateral breast cancer Any mass in contralateral breast must be proven benign by biopsy Hormone receptor status: Estrogen receptor (ER) positive or ER-negative on quantitative or qualitative assay
No prior therapy for breast cancer other than potentially curative surgery (see Disease Characteristics)
Age: See Menopausal status Sex: Female Menopausal status: Premenopausal, i.e.: Normal menstrual period within 6 months prior to entry with no prior hysterectomy and no hormone replacement therapy (HRT) Prior hysterectomy and no HRT and either age less than 40 or age 40 or greater with premenopausal luteinizing hormone, follicle-stimulating hormone, and estradiol levels On HRT and age 49 or less with menstruation within 6 months prior to starting HRT Performance status: Not specified Hematopoietic: WBC greater than 4,000/mm3 Platelet count greater than 100,000/mm3 Hepatic: Bilirubin less than 1.1 mg/dL AST less than 60 IU/L Renal: Creatinine less than 1.3 mg/dL Other: No nonmalignant systemic disease that would preclude protocol therapy or prolonged follow-up No psychiatric or addictive disorder that would preclude informed consent No prior or concurrent second malignancy except: Nonmelanomatous skin cancer Adequately treated carcinoma in situ of the cervix Not pregnant or nursing (including those who have stopped nursing within the past 6 months)
Up to 1225 patients will be accrued until mid 1999, with one additional year of follow-up.
This is a randomized, multicenter study. Patients are stratified by center, type of primary therapy, and estrogen receptor status. Patients are randomized to one of four treatment arms. Therapy begins within 6 weeks after breast surgery. Arm I: Patients receive doxorubicin (or epirubicin) plus cyclophosphamide (AC) every 21 days for 4 courses, followed immediately by cyclophosphamide, methotrexate, and fluorouracil (CMF) every 28 days for 3 courses. Arm II: Patients receive AC as in arm I, followed 16 weeks later by CMF as in arm I. Arm III: Patients receive AC and CMF as in arm I, then oral tamoxifen daily until 5 years after randomization. Arm IV: Patients receive AC and CMF as in arm II, then oral tamoxifen daily until 5 years after randomization. Patients with less than total mastectomy may receive optional radiation therapy either upon completion of all therapy or concurrently with CMF. Quality of life is assessed periodically. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and yearly thereafter. Patients who experience a recurrence in the ipsilateral conserved breast undergo either local re-excision or total mastectomy and continue on study.
Colleoni M, Gelber S, Goldhirsch A, et al.: Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node-positive breast cancer: International Breast Cancer Study Group Trial 13-93. J Clin Oncol 24 (9): 1332-41, 2006.[PUBMED Abstract]
Gianni L, Cole BF, Panzini I, et al.: Anemia during adjuvant non-taxane chemotherapy for early breast cancer: Incidence and risk factors from two trials of the International Breast Cancer Study Group. Support Care Cancer 16 (1): 67-74, 2008.[PUBMED Abstract]
Pestalozzi BC, Zahrieh D, Mallon E, et al.: Distinct clinical and prognostic features of infiltrating lobular carcinoma of the breast: combined results of 15 International Breast Cancer Study Group clinical trials. J Clin Oncol 26 (18): 3006-14, 2008.[PUBMED Abstract]
Colleoni M, Gelber S, Simoncini E, et al.: Effects of a treatment gap during adjuvant chemotherapy in node-positive breast cancer: results of International Breast Cancer Study Group (IBCSG) Trials 13-93 and 14-93. Ann Oncol 18 (7): 1177-84, 2007.[PUBMED Abstract]
Keshaviah A, Dellapasqua S, Rotmensz N, et al.: CA15-3 and alkaline phosphatase as predictors for breast cancer recurrence: a combined analysis of seven International Breast Cancer Study Group trials. Ann Oncol 18 (4): 701-8, 2007.[PUBMED Abstract]
Trial Contact Information
Trial Lead Organizations
International Breast Cancer Study 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.