Goserelin

SAN ANTONIO -- Goserelin is an attractive alternative to adjunctive chemotherapy in many women with early breast cancer, Dr. Walter Jonat said at a breast cancer symposium sponsored by the San Antonio Cancer Institute.

Monotherapy with the GnRH agonist analogue goserelin (Zoladex) displayed therapeutic efficacy equal to that of triple-drug chemotherapy but with substantially fewer side effects and better quality of life in peri- or premenopausal patients with estrogen receptor--positive, lymph node--positive breast cancer in the Zoladex Early Breast Cancer Research Association (ZEBRA) trial, reported Dr. Jonat of the University of Kiel, Germany.

ZEBRA was a 102-center controlled trial in which 1,614 pre- or perimenopausal patients underwent breast cancer surgery and were then randomized to 2 years of goserelin monotherapy or 6 months of adjunctive chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil.

After 3 years of follow-up in the Astra-Zeneca-sponsored trial, disease-free survival in the 1,189 patients with estrogen receptor--positive tumors was identical regardless of whether they received goserelin or chemotherapy. But adverse effects were much fewer with goserelin therapy.

Goserelin also proved more convenient, being given by monthly injection, while combination chemotherapy required frequent lengthy visits to the hospital or clinic.

During the 6 months that the patients were on chemotherapy, their overall quality-of-life scores, activity level, physical distress score, and effort to cope with illness were significantly worse than in the goserelin group, Dr. Jonat said.

Side effects of chemotherapy consisted chiefly of nausea, vomiting, and hair loss, while goserelin-treated patients complained of hot flashes and vaginal dryness during the 2 years that they were on the medication.

At the 6-month mark, all patients in the goserelin-treated arm were amenorrheic, as expected since the therapeutic goal was to induce a reversible medical oophorectomy. At this point two-thirds of patients in the chemotherapy arm were also amenorrheic. But their amenorrhea apparently was irreversible.

After 3 years--a full year following completion of goserelin therapy and 2 1/2 years after conclusion of chemotherapy--only one-third of the goserelin group remained amenorrheic, while 80% of the chemotherapy-treated patients had amenorrhea and vasomotor symptoms, he said.

The ZEBRA data suggest that goserelin therapy might be a better option for long-term preservation of bone mineral density although more follow-up is needed, he said.

During their 2 years of goserelin therapy, patients had greater loss of bone mineral density than did women on chemotherapy; however, posttreatment partial recovery of bone mineral density was observed in the goserelin group, while bone mineral density loss worsened in the months and years following triple-drug chemotherapy, Dr. Jonat said. (See chart.)

Disease-free survival among the subset of women with estrogen receptor-negative breast cancer was substantially better with combination chemotherapy than goserelin.

This was expected, since there's no reason to think chemical oophorectomy would have any therapeutic efficacy in tumors lacking the estrogen receptor, he said.

For ethical reasons, ZEBRA will be the last clinical trial in which estrogen receptor-negative patients are given such therapy, he said.

COPYRIGHT 2001 International Medical News Group
COPYRIGHT 2001 Gale Group