Bortezomib in combination with celecoxib in patients with advanced solid tumors: a phase I trial.
BACKGROUND
COX-2 inhibitors, such as celecoxib, and ubiquitin-proteasome pathway inhibitors, such as bortezomib, can down-regulate NF-kappaB, a transcription factor implicated in tumor growth. The objective of this study was to determine the maximum tolerated dose and dose-limiting toxicities of bortezomib in combination with celecoxib in patients with advanced solid tumors.


METHODS
Patients received escalating doses of bortezomib either on a weekly schedule (days 1, 8, 15, 22, and 29 repeated every 42 days) or on a twice-weekly administration schedule (days 1, 4, 8, and 11 repeated every 21 days), in combination with escalating doses of celecoxib twice daily throughout the study period from 200 mg to 400 mg twice daily.


RESULTS
No dose-limiting toxicity was observed during the study period. Two patients had stable disease lasting for four and five months each, and sixteen patients developed progressive disease.


CONCLUSIONS
The combination of bortezomib and celecoxib was well tolerated, without dose limiting toxicities observed throughout the dosing ranges tested, and will be studied further at the highest dose levels investigated.


BACKGROUND
NCT00290680.
Hayslip
John
J
Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina, USA. j.hayslip@uky.edu
Chaudhary
Uzair
U
Green
Mark
M
Meyer
Mario
M
Dunder
Steven
S
Sherman
Carol
C
Salzer
Shanta
S
Kraft
Andrew
A
Montero
Alberto J
AJ
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D000068579:Celecoxib; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology*; D011719:Pyrazines / Q000008:administration & dosage; D011720:Pyrazoles / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage
D001897:Boronic Acids; D011719:Pyrazines; D011720:Pyrazoles; D013449:Sulfonamides; D000069286:Bortezomib; D000068579:Celecoxib