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. boccardo@hp380.ist.unige.it.
OBJECTIVE
To compare the efficacy of chemotherapy versus that of tamoxifen plus ovarian suppression in pre-/perimenopausal estrogen receptor-positive patients with early breast cancer.


METHODS
Patients were randomly assigned to receive either six cycles of a standard regimen of cyclophosphamide 100 mg/m(2) orally days 1 to 14, methotrexate 40 mg/m(2) intravenously (IV) days 1 and 8, and fluorouracil 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 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.


CONCLUSIONS
The combination of tamoxifen with ovarian suppression seems to be safe and to yield comparable results relative to standard CMF.
Boccardo
F
F
Professorial Unit of Medical Oncology and Biostatistics Unit, University and National Cancer Institute, Genoa, Italy.
Rubagotti
A
A
Amoroso
D
D
Mesiti
M
M
Romeo
D
D
Sismondi
P
P
Giai
M
M
Genta
F
F
Pacini
P
P
Distante
V
V
Bolognesi
A
A
Aldrighetti
D
D
Farris
A
A
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D017273:Goserelin / Q000627:therapeutic use; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism; D010052:Ovariectomy; D017697:Premenopause; D011960:Receptors, Estrogen / Q000378:metabolism; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D013629:Tamoxifen; D017273:Goserelin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate