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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

By F. Boccardo, A. Rubagotti, D. Amoroso, M. Mesiti, D. Romeo, P. Sismondi, M. Giai, F. Genta, P. Pacini, V. Distante, A. Bolognesi, D. Aldrighetti, A. Farris, for the Italian Breast Cancer Adjuvant Study Group

From the Professorial Unit of Medical Oncology and Biostatistics Unit, University and National Cancer Institute, Genoa; Institute of Oncology, University of Messina, Messina; Department of Gynecologic Oncology, University and Mauriziano Hospital, Torino; Department of Gynecology and Obstetrics, Sant’Anna Gynecologic Hospital, Turin; Department of Radiotherapy, Policlinico Careggi; Department of Surgery, University of Florence, Florence; Department of Oncology–Radiotherapy, San Raffaele Hospital, Milan; and Department of Clinical Oncology, University of Sassari, Sassari, Italy.
Deceased.

Address reprint requests to Francesco Boccardo, MD, Professorial Unit of Medical Oncology, University and National Cancer Institute, Largo R. Benzi 10, 16132 Genoa, Italy; email boccardo{at}hp380.ist.unige.it

PURPOSE: To compare the efficacy of chemotherapy versus that of tamoxifen plus ovarian suppression in pre-/perimenopausal estrogen receptor–positive patients with early breast cancer.

PATIENTS AND METHODS: Patients were randomly assigned to receive either six cycles of a standard regimen of cyclophosphamide 100 mg/m² orally days 1 to 14, methotrexate 40 mg/m² intravenously (IV) days 1 and 8, and fluorouracil 600 mg/m² 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 oophorectomy, ovarian irradiation, or monthly goserelin 3.6-mg injections. Disease-free survival was the main study end point. Overall survival and toxicity were additional end points.

RESULTS: Between 1989 and 1997, 120 patients were assigned to CMF and 124 to tamoxifen and ovarian suppression (oophorectomy, n = 6; ovarian irradiation, n = 31; and goserelin injections, n = 87). At the time of analysis (median follow-up time, 76 months; range, 9 to 121 months), 82 patients had relapsed and 39 had died. No difference between groups had emerged with respect to either disease-free or overall survival. Treatments were comparable even in respect to age, tumor size, and nodal status, although a nonsignificant 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 developed benign gynecologic changes in either group, and numbers were comparable.

CONCLUSION: The combination of tamoxifen with ovarian suppression seems to be safe and to yield comparable results relative to standard CMF.

Presented in part at the Annual Meeting of the American Society of Clinical Oncology, Los Angeles, CA, May 16–19, 1998.

See Appendix for a complete list of study participants.

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