Women with hormone receptor negative breast cancer who were treated with Zoladex (goserelin) in addition to their standard chemotherapy demonstrated a reduced rate of ovarian dysfunction and ovarian failure, in addition to an increased rate of pregnancy and delivery.
For women undergoing chemotherapy there is a high risk of ovarian failure, which can result in symptoms of menopause, osteoporosis, and infertility. Embryo cryopreservation is currently an option for women who are about to undergo chemotherapy; however, this option is not suitable for all women due to factors such as cost, timing, and the need for a partner. An option explored in the current study is treatment with a GnRH agonist, Zoladex (goserelin), in an effort to preserve ovarian function.
An international phase 3 clinical trial was conducted to determine whether treating patients with Zoladex (goserelin) in addition to their chemotherapy could reduce the occurrence of ovarian failure. The study, The Prevention of Early Menopause Study (POEMS) included premenopausal women between 18 and 49 years of age who had operable stage I to IIIA estrogen receptor and progesterone receptor negative breast cancer, and were scheduled for cyclophosphamide-containing chemotherapy. At 2 years following therapy the women were assessed for ovarian dysfunction, in addition to pregnancy outcomes. A total of 218 patients were included in the study, who were randomly separated into two groups. The first group (105 patients) was given goserelin (3.6mg, every 4 weeks) in addition to their chemotherapy regimen, while the second group (113 patients) was only given chemotherapy.
In this study, ovarian failure was defined as an absence of menstruation for the previous 6 months and follicle-stimulating hormone levels similar to postmenopausal levels at 2 years. The study reported that 15 patients (22%) from the chemotherapy-only treatment group had ovarian failure, compared to 5 patients (8%) in the goserelin treatment group who had ovarian failure. Similarly, ovarian dysfunction was reported in 37% of patients in the chemotherapy-only group, compared to 23% of patients in the goserelin treatment group. After 2 years of follow up, the rate of ovarian dysfunction was 33% in the chemotherapy-only group, and 14% in the goserelin treatment group.
While the results showed that the amount of miscarriages or pregnancy complications occurred at similar rates between the two groups, there were more patients in the goserelin treatment group that had a successful delivery of at least one baby. There were 12 babies born to the women from the chemotherapy-only group, compared to 18 babies born to women from the goserelin treatment group.
Overall the study shows that Zoladex protects ovaries to some degree, reducing the risk of early menopause, while improving fertility outcomes.
Moore, HCF, Unger, JM, Phillips, K-A, Boyle, F, Hitre, E, Porter, D, Francis, PA, Goldstein, LJ, Gomez, HL, Vallejos, CS, Partridge, AH, Dakhil, SR, Garcia, AA, Gralow, J, Lombard, JM, Forbes, JF, Martino, S, Barlow, WE, Fabian, CJ, Minasian, L, Meyskens, FL, Gelber, RD, Hortobagyi, GN, Albain, KS, for the POEMS/S0230 Investigators “Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy” New England Journal of Medicine, 2015; 372:923-932 March 5, 2015 DOI: 10.1056/NEJMoa1413204.
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Written by Deborah Tallarigo, PhD