Estrogen suppression in premenopausal women following 8 weeks of treatment with exemestane and triptorelin versus triptorelin alone.
BACKGROUND
Luteinizing hormone-releasing hormone (LHRH) agonists (e.g., triptorelin) reduce ovarian estrogen production in premenopausal women with hormone-sensitive breast cancer. Aromatase inhibitors (e.g., exemestane) inhibit extraovarian production of estrogen and may further reduce circulating estrogens when combined with an LHRH agonist.


METHODS
Healthy premenopausal women were randomized to receive 3.75 mg triptorelin (T) on days 1 and 29 with 25 mg exemestane (EX) or matched placebo once daily for 8 weeks, from day 1 to day 56. The primary objective was to evaluate the effect of T +/- EX on estradiol (E(2)) suppression by comparing the AUC(day 36-57 )for the 2 treatments. Secondary objectives included evaluation of estrone (E(1)), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) suppression; effects of EX on the T-induced gonadotrophin and estrogen flare; pharmacokinetics (PK); and safety.


RESULTS
Twenty-eight (14 in each arm) were evaluable for efficacy and PK. Mean plasma estrogen levels (AUC(day 36-57)) were significantly lower for subjects who received T + EX than for subjects who received T alone (20.6 vs. 54.0 pg d/ml [-62%; P < 0.05], and 38.9 vs. 198.0 pg d/ml [-80%; P < 0.01] for E(2) and E(1), respectively). Coadministration of EX did not affect the initial flare or subsequent suppression of LH and FSH following the first dose of T, or the PK of T. Both treatments were well tolerated.


CONCLUSIONS
Coadministration of T and EX resulted in greater estrogen suppression than when T was given alone. These findings could translate into improved clinical outcomes for premenopausal breast cancer patients receiving LHRH agonists.
Jannuzzo
Maria Gabriella
MG
Nerviano Medical Sciences, Nerviano, Italy.
Di Salle
Enrico
E
Spinelli
Riccardo
R
Pirotta
Nicoletta
N
Buchan
Peter
P
Bello
Akintunde
A
D000328:Adult; D000730:Androstadienes / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D004958:Estradiol / Q000096:biosynthesis*; D004970:Estrone / Q000096:biosynthesis; D005260:Female; D006062:Gonadotropins / Q000096:biosynthesis; D006801:Humans; D010053:Ovary / Q000187:drug effects; D017697:Premenopause; D017329:Triptorelin Pamoate / Q000494:pharmacology* / Q000627:therapeutic use; D055815:Young Adult
D000730:Androstadienes; D000970:Antineoplastic Agents; D006062:Gonadotropins; D017329:Triptorelin Pamoate; D004970:Estrone; D004958:Estradiol; C056516:exemestane