Celecoxib and exemestane versus placebo and exemestane in postmenopausal metastatic breast cancer patients: a double-blind phase III GINECO study.
The aim of this study was to evaluate antitumor effects of cyclooxygenase-2 inhibitors in breast carcinoma and their ability to act synergistically with aromatase inhibitors (AIs). Postmenopausal metastatic breast cancer patients without previous adjuvant AI treatment received exemestane 25 mg/days plus either celecoxib 400 mg twice daily or placebo. The primary endpoint was progression-free survival (PFS). This trial was prematurely terminated (N = 157 of 342 planned) after cardiovascular toxicity was reported in other celecoxib trials. Although no PFS difference was observed between the two arms (9.8 months for both, P = 0.72), a trend favoring celecoxib was observed in 60 tamoxifen-resistant patients (9.6 vs. 5.1 months; P = 0.14) and in 126 patients treated >or=3 months before study termination (12.2 vs. 9.8 months; P = 0.09). No severe adverse events were reported. Cyclooxygenase-2 inhibitors seemingly contribute to reverse endocrine resistance in breast cancer patients, although further study is necessary to allow development of a new therapeutic strategy.
Falandry
C
C
Université de Lyon, 69003 Lyon, France.
Debled
M
M
Bachelot
T
T
Delozier
T
T
Crétin
J
J
Romestaing
P
P
Mille
D
D
You
B
B
Mauriac
L
L
Pujade-Lauraine
E
E
Freyer
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002318:Cardiovascular Diseases; D000068579:Celecoxib; D017024:Chemotherapy, Adjuvant; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000556:secondary; D010919:Placebos; D017698:Postmenopause; D011379:Prognosis; D011720:Pyrazoles / Q000627:therapeutic use*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000556:secondary; D013449:Sulfonamides / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
D000730:Androstadienes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D047072:Aromatase Inhibitors; D010919:Placebos; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; C056516:exemestane