GORSELIN VERUS TAMOXIFEN

Goserelin as Effective as Tamoxifen, Improves Long-Term Survival in Early Breast Cancer

February 25, 2009 — In premenopausal women with early breast cancer, adjuvant therapy with the luteinizing hormone-releasing hormone agonist goserelin (Zoladex, AstraZeneca) decreases the long-term risk for disease recurrence and death, and appears to be as effective as tamoxifen (Nolvadex, Istubal, Valodex; AstraZeneca). According to study results reported online February 24 in the Journal of the National Cancer Institute, 2 years of goserelin treatment was as effective as 2 years of tamoxifen treatment 15 years after therapy was initiated.

The largest benefit of goserelin treatment on survival and recurrence was observed in women who did not use tamoxifen, reported a multinational team of researchers. Within this subgroup, there were 13.9 fewer events per 100 women who were treated with goserelin than among those who did not receive either drug.

"It looks as though if women have 1 drug, having the other doesn't give them an additional big survival benefit," said lead author Allan Hackshaw, MSc, deputy director of Cancer Research UK and UCL Cancer Trials Centre, in London, United Kingdom. "There might indeed be a small extra benefit, but we can't say so for sure with this trial."

Although adding goserelin to tamoxifen did confer a marginal potential benefit, it did not reach statistical significance. There were 2.8 fewer events per 100 women who received both agents than among women who received tamoxifen only.

The results suggest that goserelin is a reasonable alternative to tamoxifen, especially for those who are unlikely to complete 5 years of tamoxifen therapy, and that both agents may be an option, explained Mr. Hackshaw.

"The main take-home message is that 2 years of goserelin is as effective as 2 years of tamoxifen, but also that goserelin has long-lasting benefits as much as 15 years after treatment, " he told Medscape Oncology.

Long-Term Effects Observed

Although ovarian suppression by treatment with goserelin has demonstrated a reduction in the risk for mortality among premenopausal breast cancer patients, data on the long-term benefit of this treatment is limited. The goal of the Zoladex in Premenopausal Patients (ZIPP) study was to determine whether the addition of goserelin to local treatment, with or without tamoxifen, provided a benefit in survival or recurrence among premenopausal or perimenopausal women with early breast cancer.

A total of 2706 women with breast cancer were randomized to receive goserelin (3.6 mg injection every 4 weeks), tamoxifen (20 or 40 mg daily), both drugs, or neither drug for a 2-year period. All patients first underwent primary therapy, consisting of surgery with or without radiotherapy/chemotherapy.

The median length of follow-up was 12 years, and the effect of goserelin depended primarily on whether the patient also received tamoxifen. Among patients who did not receive tamoxifen, goserelin therapy was associated with a 33% reduction in the risk for an event, a 29% reduction in risk for overall mortality, a 34% reduction in risk for disease recurrence, and a 29% reduction in risk for breast cancer mortality.

The benefit of goserelin was much smaller in patients who also received tamoxifen. Within this group, there was an 8% reduction in risk for events, a 10% reduction in risk for overall mortality, a 9% reduction in risk for recurrence, and an 11% reduction in the risk for breast cancer mortality.

Fifteen years after the initiation of treatment, the researchers observed that the number of breast cancer deaths was lower by 8.5 per 100 women in those who took goserelin alone, but was only lower by 2.6 per 100 women among those who added goserelin to tamoxifen. The latter did not meet statistical significance.

They also noted that the effect of goserelin was greatest among node-negative patients and in those with estrogen-receptor-positive tumors, and that their results were "consistent with the observation that the effect of goserelin may be greater in younger women who had prior chemotherapy."

Limitations of the trial were that patients were treated with tamoxifen for 2 years, which is currently not the standard practice, and that the trial did not address the optimal frequency and duration of goserelin treatment.