Women who received the hormone suppressor goserelin (Zoladex) along with their chemotherapy were significantly less likely to develop premature ovarian failure and were more likely to have successful pregnancies, than women who received chemotherapy alone, according to findings from the federally funded phase III S0230/POEMS clinical trial.
Emily Beard, RN, OCN, CBCN
Women who received the hormone suppressor goserelin (Zoladex) along with their chemotherapy were significantly less likely to develop premature ovarian failure and were more likely to have successful pregnancies, than women who received chemotherapy alone, according to findings from the federally funded phase III S0230/POEMS clinical trial.1 Women in the goserelin arm also were more likely to be alive 4 years after starting treatment than those in the standard-therapy arm.
“Preserving fertility is a common and important concern among younger women diagnosed with cancer, and these findings offer a simple, new option for women with breast cancer, or possibly other cancers,” said lead study author Halle Moore, MD, a staff physician at the Cleveland Clinic. “Goserelin appears to be not only highly safe but also effective, as it increased the odds of becoming pregnant and delivering a healthy baby following chemotherapy.”
Ovarian failure is a common and potentially devastating side effect of chemotherapy for breast cancer, Moore said. A woman’s risk of ovarian failure depends on the type and dose of her chemotherapy, as well as her age and perhaps ovarian cycling at the time of chemotherapy, she said.
“Potential loss of fertility is but one in a cascade of devastating realities facing young breast cancer patients, so this study—even with its limitations and unanswered questions—brings hope and promise to the conversation about fertility preservation options in the face of breast cancer,” concurred Emily Beard, RN, OCN, CBCN. Beard is Multidisciplinary Care Coordinator, Oncology Support Services, at the Northside Hospital Cancer Institute in Atlanta.
“I will never forget one such conversation with a young patient, diagnosed with early breast cancer in her mid-30s, who had started a chemotherapy regimen without fully realizing the risks it posed to her ovarian function: ‘The only thing I have ever wanted is to have children,’ this patient tearfully confided in me after being told the regimen she had been prescribed had rendered her menopausal. She was grateful to be alive, but sad: ‘I’ve lost my quality of life because now I can’t get pregnant and have a baby.’”
Goserelin and similar luteinizing hormone-releasing hormone (LHRH) analogs temporarily shut down ovarian function, essentially putting the patient into a postmenopausal state, Moore explained; it is speculated that this protects follicles from chemotherapy damage.
These medications are widely used to control ovulation timing for infertility procedures, such as in vitro fertilization, and to treat advanced prostate and breast cancer. Prior studies of this approach to preventing ovarian failure have been conducted, Moore said, but with inconclusive results and few data available on pregnancy outcomes.
Both Fertility and Survival Benefit
In this study, 257 premenopausal women aged 18 to 49 years who had stage I-IIIA estrogen- and progesterone-negative breast cancer were randomized to curative-intended treatment with either cyclophosphamide-containing chemotherapy alone (standard arm) or cyclophosphamide-containing chemotherapy plus goserelin. Goserelin was given as a monthly injection starting 1 week before the first dose of chemotherapy. Of the total study population, 218 women were evaluable, and complete primary endpoint data were available for 62% of them, the authors wrote in their abstract.
The study’s primary endpoint was the rate of ovarian failure 2 years after the start of treatment, with ovarian failure defined as no menstrual periods for the prior 6 months and postmenopausal levels of follicle-stimulating hormone (FSH). Investigators found that 8% of women in the goserelin arm versus 22% of women in the standard arm experienced ovarian failure under those criteria.
In addition, the rate of ovarian dysfunction at 2 years (defined as no menstrual periods for the prior 3 months and either FSH, estradiol, or inhibin B levels in the postmenopausal range) was reduced by close to two-thirds, with 14% of patients in the goserelin arm experiencing ovarian dysfunction compared with 33% in the control arm.” The study also found that goserelin was not associated with an increased risk of either miscarriage or pregnancy termination, ASCO noted.
Importantly, the researchers also found that goserelin improved disease-free and overall survival. They had considered those endpoints to determine whether goserelin would jeopardize the effectiveness of chemotherapy, and were surprised by the results, Moore said.
At 4 years, disease-free survival was 78% in the control group and 89% in the group that took both chemotherapy and goserelin. Four-year overall survival was 82% in the control group and 92% in the chemotherapy-plus-goserelin group.
“To date many women wishing to preserve fertility had to prioritize and accept that the choice to do so may delay initiation of chemotherapy, and therefore decrease survival,” said Beard. “There has long been controversy and concern that drugs aimed at protecting ovarian function might actually interfere with the efficacy of chemotherapy, but this study suggests that goserelin does not reduce the effectiveness of cytotoxic treatment, and it might even improve it.”
Moore noted that this study marks “the first demonstration of improved fertility and more successful pregnancies when goserelin was used. These favorable outcomes are very reassuring regarding the safety of this approach. Premenopausal women beginning therapy for early breast cancer should consider this option for prevention of premature ovarian failure.”
Beard added that the time is ripe for more research in this critical area, “especially related to what role, if any, there is for LHRH analogs in treatment regimens for other types of cancer, including perhaps hormone receptor—positive cancers.”
“As nurses we must be advocates for our patients, encouraging participation in clinical research like this so that important quality of life issues continue to be addressed.”