Prevention of chemotherapy-induced menopause by temporary ovarian suppression with goserelin in young, early breast cancer patients.
BACKGROUND
Standard methods to prevent chemotherapy-induced early menopause in young, breast cancer patients are unavailable to date. Preclinical data has suggested that luteinising hormone-releasing hormone (LH-RH) analogs given during treatment can decrease the gonado-toxicity induced by chemotherapy. This phase II study aimed to assess the activity of such a method in young, breast cancer patients undergoing adjuvant chemotherapy.


METHODS
Premenopausal patients received the LH-RH analog goserelin 3.6 mg every 4 weeks before and during chemotherapy. According to two-stage optimal phase II Simon design, treatment was considered clinically interesting if it was able to prevent menopause in 19 out of 29 patients of the study population. The resumption of ovarian function was defined by a resumption of menstrual activity or by a follicle-stimulating hormone (FSH) value < or = 40 IU/l within 12 months after the last cycle of chemotherapy.


RESULTS
Thirty patients were enrolled and 29 were evaluable. Median age was 38 years (range 29-47). All but one patient received CEF regimen (cyclophosphamide, epirubicin, 5-fluorouracil). Resumption of menstrual activity was observed in 21 patients (72%; 95% CI 52% to 87%) and a FSH value < or = 40 IU/l in 24 patients (83%; 95% CI 63% to 93%). Menses resumption was observed in 16 out of 17 patients (94%) with age <40 years and in five out of 12 patients (42%) with age > or = 40 years.


CONCLUSIONS
Goserelin given before and during chemotherapy may prevent premature menopause in the majority of patients. The different success rate by age, however, indicates the need of a prospective evidence of the efficacy of such a strategy.
Del Mastro
L
L
Oncologia Medica, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. lucia.delmastro@istge.it
Catzeddu
T
T
Boni
L
L
Bell
C
C
Sertoli
M R
MR
Bighin
C
C
Clavarezza
M
M
Testa
D
D
Venturini
M
M
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000009:adverse effects; D003561:Cytarabine / Q000009:adverse effects; D015251:Epirubicin / Q000009:adverse effects; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism; D017273:Goserelin / Q000627:therapeutic use*; D006801:Humans; D008593:Menopause / Q000187:drug effects*; D008594:Menopause, Premature; D008597:Menstrual Cycle; D008875:Middle Aged; D010053:Ovary / Q000187:drug effects*; D017697:Premenopause / Q000187:drug effects; D011446:Prospective Studies
D018931:Antineoplastic Agents, Hormonal; D003561:Cytarabine; D017273:Goserelin; D015251:Epirubicin; D004958:Estradiol; D003520:Cyclophosphamide; D005640:Follicle Stimulating Hormone