Temporary ovarian suppression with goserelin for prevention of chemotherapy-induced menopause in young early breast cancer patients: Results of a phase II study

Abstract

662 Background: Early menopause is a frequent irreversible side-effect induced by chemotherapy(CT) in young patients(pts) and no standard methods for its prevention are available. Preclinical data suggests that LHRH analogs given during CT can decrease gonado-toxicity induced by CT. The aim of this trial was to investigate the ability of Goserelin(G) to prevent CT-induced menopause by a two-step phase II study. Methods: Treatment with G was considered clinically interesting if it was able to prevent menopause in at least 80% of pts whilst the accrual was stopped with a success rate <50%. The planned sample size was 29 pts. End point of the study was resumption of menstrual activity(MA) and/or a FSH value <40IU/L within 12 months after the CT end. FSH, LH and E2 were assessed at 3, 6, 9 and 12 months after the end of CT and then every 6 months. G 3.6 mg was administered at least 1 wk before CT and then every 4 wks until CT completion. Results: From Oct 2001 to Jun 2003, 30 pts were enrolled and 29 were evaluable. Median age was 38(29–47); 11(38%) pts had no previous pregnancy. All but one patient(96%) received FEC regimen; median number of CT cycles: 6(5–8), median number of G doses: 5(2–6). After CT, all ER+ and/or PgR+ pts received tamoxifen. Within 12 months after the end of CT resumption of ovarian activity(OA) was indicated by: 1)both a FSH level ≤40 and resumed MA in 17 pts(58.6%); 2)FSH ≤40 without resumption of MA but with premenopausal E2 level(>20 pg/mL) in 4 pts(13.7%); 3)resumption of MA but not available data on FSH and E2 in 3 pts(10%); 4)FSH ≤40 but without E2 increase and no resumption of MA in 3 pts(10%). One patient with both FSH>40 and E2<20 had a single menstrual mense 12 months after CT end, but no further signs of OA were reported in the follow-up. One patient who stopped CT after 1 cycle and continued G as antitumor therapy was not evaluable and was considered a failure. Median time to menstrual resumption was 164 days(63–362). Conclusions: After treatment with G given prior and during CT a sure ovarian function resumption (FSH ≤40 + MA or FSH ≤40 + increased E2 or MA and FSH and E2 levels unknown) was observed in 83% of pts. Ovarian function resumption was uncertain in 10% pts. No significant financial relationships to disclose.