Safety of prolonged therapy with bortezomib in relapsed or refractory multiple myeloma.
BACKGROUND
Bortezomib, a first-in-class proteasome inhibitor, is active with manageable toxicities in relapsed and/or refractory myeloma.


METHODS
Bortezomib 1.0 or 1.3 mg/m2 was administered Days 1, 4, 8, and 11 every 21 days for up to 8 cycles to patients with relapsed and/or refractory myeloma participating in two Phase II trials. Dexamethasone could be added because of progressive disease after 2 cycles or stable disease after 4 cycles. Continuation of or retreatment with bortezomib was offered to patients who, in the investigator's opinion, would benefit from extended treatment.


RESULTS
Sixty-three patients with relapsed/refractory myeloma treated in this extension trial received a median of 7 additional cycles of therapy, for a total of 14 cycles (range, 7-32) over a median duration of therapy of 45.1 weeks in the parent and extension studies. Seventy-eight percent of patients completed this study at the same or higher bortezomib dose than they started on during this study, and the treatment schedule of twice-weekly administration remained unchanged in 89%. Overall, 75% of patients received dexamethasone in combination with bortezomib for a median of 5 cycles starting either in the parent or extension study. The safety profile was similar between the extension and parent trials, with no evidence of new cumulative toxicity. The most commonly reported Grade 3/4 toxicities were thrombocytopenia (29%), with a consistent pattern of recovery during the rest period of each cycle, diarrhea (11%), anemia (11%), and neutropenia (10%). Neuropathy was reported less frequently.


CONCLUSIONS
Retreatment with or continuation of bortezomib +/- dexamethasone beyond 6 months was safe, and toxicities were manageable, in patients with relapsed and/or refractory myeloma.
Berenson
James R
JR
Institute for Myeloma Bone Cancer Research, West Hollywood, California 90069, USA. jberenson@myelomasource.org
Jagannath
Sundar
S
Barlogie
Bart
B
Siegel
David T
DT
Alexanian
Raymond
R
Richardson
Paul G
PG
Irwin
David
D
Alsina
Melissa
M
Rajkumar
S Vincent
SV
Srkalovic
Gordon
G
Singhal
Seema
S
Limentani
Steven
S
Niesvizky
Ruben
R
Esseltine
Dixie L
DL
Trehu
Elizabeth
E
Schenkein
David P
DP
Anderson
Kenneth
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D003907:Dexamethasone / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011719:Pyrazines / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone