Bortezomib in combination with dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma with less than optimal response to bortezomib alone.
OBJECTIVE
The efficacy and safety of added dexamethasone were assessed in patients with relapsed and/or refractory multiple myeloma who had a suboptimal response to bortezomib alone.


METHODS
In two previously reported, open-label, multicenter phase 2 studies, bortezomib 1.0 or 1.3 mg/m2 was administered intravenously twice weekly for 2 weeks of a 3-week cycle for up to 8 cycles to patients who had failed either > or = 2 lines of therapy (SUMMIT, n=202) or first-line therapy (CREST, n=54). Patients with progressive disease after the first two cycles or stable disease after four cycles of bortezomib were eligible for addition of oral dexamethasone 20 mg on the day of and after each bortezomib dose. Responses were assessed by an Independent Review Committee using European Group for Blood and Marrow Transplantation criteria.


RESULTS
Addition of dexamethasone to bortezomib was associated with improved responses in 13 of 74 evaluable patients (18%) in SUMMIT and 9 of 27 (33%) in CREST; eight of these 22 patients had been previously refractory to dexamethasone. There were 2 complete, 8 partial, and 12 minimal responses. Dexamethasone did not appear to alter the type or number of adverse events. Treatment-emergent adverse events reported in > or = 20% of patients receiving combination therapy were fatigue (25%), thrombocytopenia (24%), insomnia (21%), and nausea (20%).


CONCLUSIONS
Addition of dexamethasone to bortezomib in patients with relapsed and/or refractory myeloma who had suboptimal responses to bortezomib alone was associated with improvement in responses without prohibitive toxicity.
Jagannath
Sundar
S
St. Vincent's Comprehensive Cancer Center, 325 West 15th Street, New York, NY, USA. sjagannath@aptiumoncology.com
Richardson
Paul G
PG
Barlogie
Bart
B
Berenson
James R
JR
Singhal
Seema
S
Irwin
David
D
Srkalovic
Gordan
G
Schenkein
David P
DP
Esseltine
Dixie L
DL
Anderson
Kenneth C
KC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D011719:Pyrazines / Q000008:administration & dosage*; D016879:Salvage Therapy / Q000379:methods; D016896:Treatment Outcome
D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone