Halle C F Moore1, Joseph M Unger, Kelly-Anne Phillips, Frances Boyle, Erika Hitre, David Porter, Prudence A Francis, Lori J Goldstein, Henry L Gomez, Carlos S Vallejos, Ann H Partridge, Shaker R Dakhil, Agustin A Garcia, Julie Gralow, Janine M Lombard, John F Forbes, Silvana Martino, William E Barlow, Carol J Fabian, Lori Minasian, Frank L Meyskens, Richard D Gelber, Gabriel N Hortobagyi, Kathy S Albain. 1. From the Cleveland Clinic Foundation, Cleveland (H.C.F.M.); SWOG Cancer Research Group Statistical Center, Fred Hutchinson Cancer Research Center (J.M.U., W.E.B.), and Seattle Cancer Care Alliance and University of Washington (J.G.) - all in Seattle; Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC (K.-A.P., P.A.F.), Australia and New Zealand Breast Cancer Trials Group (ANZBCTG) (K.-A.P., P.A.F., J.F.F.), Calvary Mater Hospital, Newcastle, NSW (F.B., J.M.L., J.F.F.), and University of Sydney, Sydney (F.B.) - all in Australia; International Breast Cancer Study Group (IBCSG), Bern, Switzerland (K.-A.P., P.A.F.); National Institute of Oncology, Budapest, Hungary (E.H.); Auckland Regional Cancer and Blood Service, Auckland, New Zealand (D.P.); Fox Chase Cancer Center, Philadelphia (L.J.G.); Instituto de Enfermedades Neoplasicas (H.L.G.) and Oncosalud SAC (C.S.V.), Lima, Peru; Dana-Farber Cancer Institute (A.H.P., R.D.G.) and IBCSG Statistical Center (R.D.G.) - both in Boston; Wichita Community Clinical Oncology Program, Wichita (S.R.D.), and University of Kansas, Westwood (C.J.F.) - both in Kansas; University of Southern California Norris Cancer Center, Los Angeles (A.A.G.), the Angeles Clinic and Research Institute, Santa Monica (S.M.), and University of California at Irvine Chao Family Comprehensive Cancer Center, Orange (F.L.M) - all in California; National Cancer Institute, Division of Cancer Prevention, Bethesda, MD (L.M.); M.D. Anderson Cancer Center, Houston (G.N.H.); and Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, IL (K.S.A.).
Abstract
BACKGROUND: Ovarian failure is a common toxic effect of chemotherapy. Studies of the use of gonadotropin-releasing hormone (GnRH) agonists to protect ovarian function have shown mixed results and lack data on pregnancy outcomes. METHODS: We randomly assigned 257 premenopausal women with operable hormone-receptor-negative breast cancer to receivestandard chemotherapy with the GnRH agonist goserelin (goserelin group) or standard chemotherapy without goserelin (chemotherapy-alone group). The primary study end point was the rate of ovarian failure at 2 years, with ovarian failure defined as the absence of menses in the preceding 6 months and levels of follicle-stimulating hormone (FSH) in the postmenopausal range. Rates were compared with the use of conditional logistic regression. Secondary end points included pregnancy outcomes and disease-free and overall survival. RESULTS: At baseline, 218 patients were eligible and could be evaluated. Among 135 with complete primary end-point data, the ovarian failure rate was 8% in the goserelin group and 22% in the chemotherapy-alone group (odds ratio, 0.30; 95% confidence interval [CI], 0.09 to 0.97; two-sided P=0.04). Owing to missing primary end-point data, sensitivity analyses were performed, and the results were consistent with the main findings. Missing data did not differ according to treatment group or according to the stratification factors of age and planned chemotherapy regimen. Among the 218 patients who could be evaluated, pregnancy occurred in more women in the goserelin group than in the chemotherapy-alone group (21% vs. 11%, P=0.03); women in the goserelin group also had improved disease-free survival (P=0.04) and overall survival (P=0.05). CONCLUSIONS: Although missing data weaken interpretation of the findings, administration of goserelin with chemotherapy appeared to protect against ovarian failure, reducing the risk of early menopause and improving prospects for fertility. (Funded by the National Cancer Institute and others; POEMS/S0230 ClinicalTrials.gov number, NCT00068601.).
RCT Entities:
BACKGROUND:Ovarian failure is a common toxic effect of chemotherapy. Studies of the use of gonadotropin-releasing hormone (GnRH) agonists to protect ovarian function have shown mixed results and lack data on pregnancy outcomes. METHODS: We randomly assigned 257 premenopausal women with operable hormone-receptor-negative breast cancer to receive standard chemotherapy with the GnRH agonist goserelin (goserelin group) or standard chemotherapy without goserelin (chemotherapy-alone group). The primary study end point was the rate of ovarian failure at 2 years, with ovarian failure defined as the absence of menses in the preceding 6 months and levels of follicle-stimulating hormone (FSH) in the postmenopausal range. Rates were compared with the use of conditional logistic regression. Secondary end points included pregnancy outcomes and disease-free and overall survival. RESULTS: At baseline, 218 patients were eligible and could be evaluated. Among 135 with complete primary end-point data, the ovarian failure rate was 8% in the goserelin group and 22% in the chemotherapy-alone group (odds ratio, 0.30; 95% confidence interval [CI], 0.09 to 0.97; two-sided P=0.04). Owing to missing primary end-point data, sensitivity analyses were performed, and the results were consistent with the main findings. Missing data did not differ according to treatment group or according to the stratification factors of age and planned chemotherapy regimen. Among the 218 patients who could be evaluated, pregnancy occurred in more women in the goserelin group than in the chemotherapy-alone group (21% vs. 11%, P=0.03); women in the goserelin group also had improved disease-free survival (P=0.04) and overall survival (P=0.05). CONCLUSIONS: Although missing data weaken interpretation of the findings, administration of goserelin with chemotherapy appeared to protect against ovarian failure, reducing the risk of early menopause and improving prospects for fertility. (Funded by the National Cancer Institute and others; POEMS/S0230 ClinicalTrials.gov number, NCT00068601.).
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