SAN ANTONIOThe gonadotropin hormone-releasing hormone
agonist analog goserelin (Zoladex) is an alternative to adjuvant chemotherapy
for women with early breast cancer who are pre- or perimenopausal and have
estrogen-receptor (ER)-positive tumors, said Walter Jonat, MD, of the
University of Kiel, Germany. He spoke at the 23rd Annual San Antonio Breast
Cancer Symposium on behalf of the Zoladex Early Breast Cancer Research
The survival results in ER-positive and ER-negative patients
were analyzed separately. In ER-positive patients, goserelin was found to be
equivalent to cyclophosphamide, methotrexate and fluorouracil (CMF) in terms
of disease-free survival (hazard ratio, 0.99) but without chemotherapy’s
harsh side effects.
Overall survival with goserelin in the ER-positive patients
mirrors that of CMF, but mature data are needed to verify this finding, Dr.
In ER-negative-patients, as expected, the hazard ratio for
disease-free survival was in favor of CMF (1.72).
The study followed 1,640 women from 102 centers in 15 countries
who were enrolled between October 1, 1990 and December 30, 1996. Patients were
randomized to receive either 3.6 mg of goserelin (n = 817) or six cycles of CMF
(n = 823). Prognostic factors were well balanced between the groups.
Bone Mineral Density
Patients who received goserelin had better long-term
preservation of bone mineral density (BMD). Bone mineral density was lost
during treatment in both groups, but was partially recovered in the goserelin
patients after treatment was finished. In contrast, the CMF patients
experienced ongoing BMD loss after the conclusion of treatment.
"Ovarian suppression resulting in amenorrhea is associated
with bone mineral density loss," Dr. Jonat said.
About 95% of patients who received goserelin became amenorrheic
during the 2-year treatment period. In contrast, 60.2% and 71.7% of the CMF
patients were amenorrheic at 24 weeks and 2 years, respectively. However, at 3
years, menses had returned in the majority of patients taking goserelin, and
only 37.8% were amenorrheic. By comparison, 79% of patients who received CMF
were amenorrheic at 3 years.
Patients who received goserelin also reported significantly
better scores for overall quality of life, as well as activity level, physical
distress, and efforts to cope with illness at 3 and 6 months when compared with
patients who received CMF. This coincides with the CMF treatment period.
However, no significant difference in overall quality of life between the two
groups was seen after 6 months, Dr. Jonat commented.
Patients ranked the two therapies as comparable for
psychological distress and social effects. In evaluations of hormonal effects
(hot flushes and vaginal dryness) over the first 2 years, women scored CMF
significantly better than goserelin, but at 3 years, after the conclusion of
goserelin treatment, that finding was reversed, with goserelin rated better.