Leuprorelin acetate every-3-months depot versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant treatment in premenopausal patients with node-positive breast cancer: the TABLE study.

PURPOSE: Ovarian suppression with luteinizing hormone-releasing hormone (LHRH) agonists is an effective adjuvant treatment for premenopausal women with estrogen receptor (ER) -positive breast cancer. Whereas monthly LHRH agonist therapy has been well established, the value of every-3-months (3-monthly) formulations is unclear. PATIENTS AND METHODS: This randomized phase III trial was performed to compare the 3-monthly depot LHRH agonist leuprorelin acetate (LAD-3M; n = 299) and chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF; n = 300) in pre- or perimenopausal patients with ER-positive, node-positive breast cancer. RESULTS: With a median follow-up of 5.8 years, recurrence-free survival was similar for patients treated with LAD-3M or CMF (hazard ratio [HR], 1.19; 95% CI, 0.94 to 1.51; P = .15). There was no substantial heterogeneity in the relative treatment effect among subgroups defined by age, progesterone receptor (PR) status, nodal status, hormone levels, or menstrual recovery after treatment. Exploratory overall survival analysis favored LAD-3M (HR, 1.50; 95% CI, 1.13 to 1.99; P = .005). Chemotherapy-related adverse effects such as nausea, vomiting, and alopecia were more common with CMF, whereas symptoms of estrogen suppression such as hot flushes and sweating were initially more pronounced with LAD-3M. CONCLUSION: The 3-monthly depot LHRH-agonist leuprorelin acetate is an effective adjuvant treatment in premenopausal patients with hormone receptor-positive, node-positive breast cancer that is not inferior to CMF.

Cyclophosphamide, methotrexate and fluorouracil (CMF) versus hormonal ablation with leuprorelin acetate as adjuvant treatment of node-positive, premenopausal breast cancer patients: preliminary results of the TABLE-study (Takeda Adjuvant Breast cancer study with Leuprorelin Acetate).

PURPOSE: The objective of this study was to evaluate the efficacy and tolerability of leuprorelin acetate in adjuvant treatment in comparison to standard chemotherapy with CMF in premenopausal, estrogen-receptor-positive or unknown, node-positive patients with early breast cancer. PATIENTS AND METHODS: The patients were randomly assigned to receive either 2 years of hormone ablation with leuprorelin acetate 11.25 mg as a subcutaneous injection every three months or six courses of CMF (cyclophosphamide 500 mg/m2, methotrexate 40 mg/m2, fluorouracil 600 mg/m2, days 1 and 8, q 4 weeks). The primary study end-point was recurrence-free survival (RFS) after 2 years. Secondary end-points included overall survival, adverse events and hormonal suppression. RESULTS: Between 1995 and 1999, a total of 589 patients with breast cancer were randomized to treatment with leuprorelin acetate or CMF. The data of 227 patients were available for this first interim analysis. One hundred and ten and 117 patients were assigned to leuprorelin acetate and chemotherapy, respectively. Both treatment arms were well balanced for baseline characteristics. So far, no difference between the groups has emerged with respect to recurrence-free or overall survivaL Suppression of serum estradiol levels and menstruation was less marked in the CMF-group compared to the leuprorelin arm. The most common adverse events were low-grade hot flushes, weight gain and increased sweating in the leuprorelin-treated patients and alopecia, nausea and vomiting in the CMF-group. CONCLUSION: According to these preliminary results, ovarian suppression with leuprorelin acetate was as effective as standard chemotherapy for premenopausal women with hormone-sensitive, node-positive early breast cancer.