NEW ORLEANSPremenopausal women with breast cancer who receive goserelin(Drug information on goserelin) (Zoladex) have an increased event-free survival over 5 years, regardless of whether they also receive tamoxifen(Drug information on tamoxifen) (Nolvadex) or have had prior chemotherapy. This key finding from 5-year follow-up of the Zoladex in Premenopausal Patients (ZIPP) trial was presented at the 36th Annual Meeting of the American Society of Clinical Oncology (ASCO).
The ZIPP trial, initiated in 1995, was designed to study the effect of goserelin as an addition to standard treatments in premenopausal women, and to determine whether it influenced relapse-free survival. The study is also investigating goserelins efficacy in conjunction with tamoxifen.
Findings from the 5-year follow-up data from the study were presented in a poster by Joan Houghton, MD, Cancer Research Campaign (CRC) and UCL Cancer Trials Center, London.
Goserelin is a luteinizing hormone releasing hormone (LHRH) agonist that suppresses ovarian estrogen production, and results in amenorrhea that is reversible on discontinuation. The drug was initially approved in 1990 for the treatment of endometriosis.
A total of 2,710 patients with early-stage breast cancer were recruited into the study. They had a median age of 44.6 years; 42% were node positive, 43% received adjuvant chemotherapy (primarily the node-positive patients), and 32% had elective tamoxifen. Of 2,106 patients who had known receptor status, 70% were estrogen-receptor (ER) positive.
After surgery, patients were randomized into one of four treatment groups. The first consisted of 469 patients who received goserelin (3.6 mg every 4 weeks for 2 years). The second, 880 patients, received tamoxifen (20 or 40 mg/d for 2 years). The third group, 885 patients, received both goserelin and tamoxifen. The fourth group consisted of 476 controls who did not receive any adjuvant hormone therapy.
Researchers at participating centers were given a choice as to whether they wanted to randomize women for tamox-ifen treatment or give it electively.
Patients were followed for an average of 5.5 years. The goserelin group (with or without tamoxifen) included 1,315 evaluable patients, while the no-goserelin control group (no adjuvant therapy or tamoxifen only) had 1,333 evaluable patients.
Patients who were treated with goserelin had significantly better recurrence-free survival than patients who did not receive the drug, Dr. Houghton said. This difference remained regardless of whether the women also got tamoxifen or had prior chemotherapy.
A univariate analysis found no advantage in relapse-free survival with tam-oxifen; patients who received the drug had a relative risk of 0.91, Dr. Houghton said. This compares to a relative risk of 0.77 in patients who received goserelin, a 23% risk reduction.
Also, among patients taking goserelin, there was a trend toward longer overall survival (relative risk, 0.78).
Dr. Houghton reported 330 first events (local recurrence, distant recurrence, new primary tumor, or non-breast-cancer death) in the goserelin group, and 411 among the no-goserelin controls.
Also, 117 patients in the goserelin group had local recurrence, compared with 163 in the control group. Another 179 in the treatment group had distant recurrence, compared with 199 in the control group. In addition, among those who received goserelin, 29 developed new primary tumors, compared with 46 of the controls.
On univariate analysis, the following factors were found to have a significant influence on relapse-free survival: nodal status, ER status, age, and surgical operation (as an indicator of the extent of local disease). The researchers developed a Cox model including these variables as well as those for treatment and for interactions with ER status.
In this model, subgroup analyses showed that, to date, patients over the age of 40 have a significant benefit in relapse-free survival (relative risk, 0.75). The benefit in younger women was not significant (relative risk, 0.83).
Patients with ER-positive tumors had increased benefit with the drug (relative risk for relapse-free survival, 0.71).
Dr. Houghton concluded that the significant advantage conferred by goserelin in the trial suggests that the drug may provide a new adjuvant therapy choice for premenopausal breast cancer patients. She cautioned, however: Well need to await results from other trials of chemotherapy and Zoladex to validate this.