Treatment of advanced hormone-sensitive breast cancer in postmenopausal women with exemestane alone or in combination with celecoxib.
OBJECTIVE
Preclinical data showed that the combination of exemestane and celecoxib has synergistic effects. Therefore, a study was undertaken to explore the efficacy and tolerability of this combination in postmenopausal patients with advanced, hormone-sensitive breast cancer.


METHODS
A randomized phase II study was conducted in postmenopausal patients with hormone-sensitive breast cancer and measurable disease who had progressive disease after treatment with tamoxifen. Patients were randomly assigned to either exemestane 25 mg daily or the combination of exemestane 25 mg daily with celecoxib 400 mg twice daily. Response Evaluation Criteria in Solid Tumors Group criteria were used to determine antitumor efficacy. Primary end point was the rate of clinical benefit. Secondary end points were tolerability, objective response rate, time to progression (TTP), and duration of clinical benefit. A pharmacodynamic and a pharmacokinetic study were conducted in parallel.


RESULTS
One hundred eleven patients (exemestane, n = 55; combination, n = 56) were enrolled in 2002. The demographic characteristics and prognostic factors were similar in both arms. In the assessable population, 24 of 51 patients in the combination arm and 24 of 49 patients in the exemestane arm achieved clinical benefit. TTP was similar in both groups. Duration of clinical benefit was longer in the combination group (median, 96.6 v 49.1 weeks). The addition of celecoxib did not change the tolerability profile of exemestane alone.


CONCLUSIONS
Similar rates of clinical benefit were achieved in both groups.
Dirix
Luc Yves
LY
Medical Oncology Unit, Oncologisch Centrum Sint-Augustinus, Oosterveldlaan 24, 2610 Wilrijk, Belgium. luc.dirix@gvagroup.be
Ignacio
Jorge
J
Nag
Shona
S
Bapsy
Poonamally
P
Gomez
Henry
H
Raghunadharao
Digumarti
D
Paridaens
Robert
R
Jones
Stephen
S
Falcon
Silvia
S
Carpentieri
Marina
M
Abbattista
Antonello
A
Lobelle
Jean-Pierre
JP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000188:drug therapy*; D000068579:Celecoxib; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D017698:Postmenopause; D011720:Pyrazoles / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage; D014018:Tissue Distribution; D016896:Treatment Outcome
D000730:Androstadienes; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; C056516:exemestane