Cyclophosphamide, methotrexate, and fluorouracil versus tamoxifen plus ovarian suppression as adjuvant treatment of estrogen receptor-positive pre-/perimenopausal breast cancer patients: Results of the Italian Breast Cancer Adjuvant Study Group 02 Randomized Trial

Purpose: To compare the efficacy of chemotherapy versus that of tamoxifen p lus ovarian suppression in pre-/perimenopausal estrogen receptor-positive p atients with early breast cancer. Patients and Methods: Patients were randomly assigned to receive either six cycles of a standard regimen of cyclophasphamide 100 mg/m(2) orally days 1 to 14, methotrexate 40 mg/m2 intravenously (IV) days 1 and 8, and fluorour acil 600 mg/m(2) IV days 1 and 8 (CMF), with all drugs restarted on day 29, or 5 years of tamoxifen, 30 mg/d, plus ovarian suppression with surgical o ophorectomy, ovarian irradiation, or monthly goserelin 3.6-mg injections. D isease-free survival was the main study end point. Overall survival and tox icity were additional end points. Results: Between 1989 and 1997, 120 patients were assigned to CMF and 124 t o tamoxifen and ovarian suppression (oophorectomy, n = 6; ovarian irradiati on, n=31; and goserelin injections, n = 87). At the rime of analysis (media n follow-up time, 76 months; range, 9 to 121 months), 82 patients had relap sed and 39 had died. No difference between groups held emerged with respect to either disease-free or overall survival, Treatments were comparable eve n in respect to age, tumor size, and nodal status, although a nonsignifican t trend favored patients with poorly differentiated tumors treated with CMF , Leukopenia, nausea, vomiting, stomatitis, and alopecia were significantly more common in patients treated with CMF. There were few patients who deve loped benign gynecologic changes in either group, and numbers were comparab le. Conclusion: The combination of tamoxifen with ovarian suppression seems to be safe and to yield comparable results relative to standard CMF. (C) 2000 by American Society of Clinical Oncology.