title: Effect of the gonadotropin-releasing hormone analogue triptorelin on the occurrence of chemotherapy-induced early menopause in premenopausal women with breast cancer: a randomized trial.
abstract: BACKGROUND
  Premenopausal patients with breast cancer are at high risk of premature ovarian failure induced by systemic treatments, but no standard strategies for preventing this adverse effect are yet available.
  
  
  OBJECTIVE
  To determine the effect of the temporary ovarian suppression obtained by administering the gonadotropin-releasing hormone analogue triptorelin during chemotherapy on the incidence of early menopause in young patients with breast cancer undergoing adjuvant or neoadjuvant chemotherapy.
  
  
  METHODS
  The PROMISE-GIM6 (Prevention of Menopause Induced by Chemotherapy: A Study in Early Breast Cancer Patients-Gruppo Italiano Mammella 6) study, a parallel, randomized, open-label, phase 3 superiority trial, was conducted at 16 sites in Italy and enrolled 281 patients between October 2003 and January 2008. The patients were premenopausal women with stage I through III breast cancer who were candidates for adjuvant or neoadjuvant chemotherapy. Assuming a 60% rate of early menopause in the group treated with chemotherapy alone, it was estimated that 280 patients had to be enrolled to detect a 20% absolute reduction in early menopause in the group treated with chemotherapy plus triptorelin. The intention-to-treat analysis was performed by including all randomized patients and using imputed values for missing data.
  
  
  METHODS
  Before beginning chemotherapy, patients were randomly allocated to receive chemotherapy alone or combined with triptorelin. Triptorelin was administered intramuscularly at a dose of 3.75 mg at least 1 week before the start of chemotherapy and then every 4 weeks for the duration of chemotherapy.
  
  
  METHODS
  Incidence of early menopause (defined as no resumption of menstrual activity and postmenopausal levels of follicle-stimulating hormone and estradiol 1 year after the last cycle of chemotherapy).
  
  
  RESULTS
  The clinical and tumor characteristics of the 133 patients randomized to chemotherapy alone and the 148 patients randomized to chemotherapy plus triptorelin were similar. Twelve months after the last cycle of chemotherapy (last follow-up, August 18, 2009), the rate of early menopause was 25.9% in the chemotherapy-alone group and 8.9% in the chemotherapy plus triptorelin group, an absolute difference of -17% (95% confidence interval, -26% to -7.9%; P < .001). The odds ratio for treatment-related early menopause was 0.28 (95% confidence interval, 0.14 to 0.59; P < .001).
  
  
  CONCLUSIONS
  The use of triptorelin-induced temporary ovarian suppression during chemotherapy in premenopausal patients with early-stage breast cancer reduced the occurrence of chemotherapy-induced early menopause.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00311636.
authors.affiliation: S. S. Sviluppo Terapie Innovative, Oncologia Medica A, Istituto Nazionale per la Ricerca sul Cancro, L.go R. Benzi 10, 16132 Genova, Italy. lucia.delmastro@istge.it
authors.forename: Lucia
authors.initials: L
authors.lastname: Del Mastro
authors.forename: Luca
authors.initials: L
authors.lastname: Boni
authors.forename: Andrea
authors.initials: A
authors.lastname: Michelotti
authors.forename: Teresa
authors.initials: T
authors.lastname: Gamucci
authors.forename: Nina
authors.initials: N
authors.lastname: Olmeo
authors.forename: Stefania
authors.initials: S
authors.lastname: Gori
authors.forename: Monica
authors.initials: M
authors.lastname: Giordano
authors.forename: Ornella
authors.initials: O
authors.lastname: Garrone
authors.forename: Paolo
authors.initials: P
authors.lastname: Pronzato
authors.forename: Claudia
authors.initials: C
authors.lastname: Bighin
authors.forename: Alessia
authors.initials: A
authors.lastname: Levaggi
authors.forename: Sara
authors.initials: S
authors.lastname: Giraudi
authors.forename: Nicola
authors.initials: N
authors.lastname: Cresti
authors.forename: Emanuela
authors.initials: E
authors.lastname: Magnolfi
authors.forename: Tiziana
authors.initials: T
authors.lastname: Scotto
authors.forename: Carlo
authors.initials: C
authors.lastname: Vecchio
authors.forename: Marco
authors.initials: M
authors.lastname: Venturini
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D017273:Goserelin / Q000627:therapeutic use; D006801:Humans; D007247:Infertility, Female / Q000517:prevention & control*; D007273:Injections, Intramuscular; D008186:Luteolytic Agents / Q000627:therapeutic use*; D008593:Menopause / Q000187:drug effects*; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D017697:Premenopause; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced* / Q000517:prevention & control*; D013629:Tamoxifen / Q000627:therapeutic use; D017329:Triptorelin Pamoate / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D008186:Luteolytic Agents; D017329:Triptorelin Pamoate; D013629:Tamoxifen; D017273:Goserelin; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate