Tamoxifen Plus Goserelin as Adjuvant Therapy

VIENNA, Austria—In a group of estrogen- or progesterone-positive breast cancer patients, combination endocrine treatment using goserelin (Zoladex) and tamoxifen (Nolvadex) significantly reduced the number of recurrences and increased disease-free survival, compared with CMF, after a median follow-up of 4 years, said Reimond Jakesz, MD, of the Department of General Surgery, University of Vienna, Austria.

“Most significant is a reduction in the number of local recurrences by more than 50% after endocrine treatment, especially since 60% of the patients in the study had breast-conserving surgery,” Dr. Jakesz said at the 35th annual meeting of the American Society of Clinical Oncology (ASCO) in Atlanta.

Dr. Jakesz reported results of the Austrian Breast Cancer Study Group (ABCSG) Trial 5, a trial involving 1,045 premenopausal breast cancer patients with hormone-responsive stage I and II disease. The trial was conducted at 65 centers throughout Austria.

The study, initiated in 1990, randomized patients to receive the endocrine combination—tamoxifen (20 mg orally) for 5 years plus goserelin (3.6 mg subcutaneously) every 28 days for 3 years—or six cycles of standard CMF—cyclophosphamide, 600 mg/m2; methotrexate, 40 mg/m²; and fluorouracil, 600 mg/m²—IV on days 1 and 8. They were observed for a median of 4 years.

A total of 167 recurrences (53 local) and 68 deaths were recorded within the follow-up period. Roughly 14% of the patients on the tamoxifen/goserelin combination experienced a recurrence, compared with 18% in the CMF group. Four patients on tamoxifen/goserelin had a contralateral breast cancer, compared with nine in the CMF group. In the endocrine combination group, 3.1% had a local recurrence vs 7.1% on CMF. Also, there were 29 deaths on the endocrine combination, compared with 39 on CMF.

To sum up, Dr. Jakesz noted that patients treated with the combination of goserelin and tamoxifen showed a significantly improved disease-free survival, compared with CMF (P < .02). The trend favoring the endocrine combination was not statistically significant for overall survival, however.

Patients treated with breast conservation surgery and radiation (about 60% of the patients) had a 4.6-fold risk of developing a local recurrence if taking CMF, compared with the patients on endocrine treatment. “We saw excellent local control of patients treated by endocrine therapy,” Dr. Jakesz said.

With respect to progesterone-receptor levels, analysis showed that patients with a higher number of progesterone receptors had about one third the risk of developing a recurrence, compared with other progesterone groups, he said. There was no such interaction in the CMF-treated group.

‘Endocrine Therapy Less Toxic’

Patients reported a total of 21,000 episodes of side effects during outpatient visits. According to Dr. Jakesz, these were as expected: stomatitis, nausea, diarrhea, fever, and infection in the CMF group; and headache, vertigo, and hot flashes among patients on the tamoxifen/goserelin combination. Dr. Jakesz said, “The endocrine treatment appears to be less toxic and better tolerated than chemotherapy, with significantly better treatment adherence.”

Dr. Jakesz underscored that although these findings are preliminary, the data indicate a significant benefit for the tamoxifen/goserelin combination, compared with CMF.