A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma.
In a phase 2 open-label study of the novel proteasome inhibitor bortezomib, 54 patients with multiple myeloma who had relapsed after or were refractory to frontline therapy were randomized to receive intravenous 1.0 or 1.3 mg/m(2) bortezomib twice weekly for 2 weeks, every 3 weeks for a maximum of eight cycles. Dexamethasone was permitted in patients with progressive or stable disease after two or four cycles respectively. Responses were determined using modified European Group for Blood and Marrow Transplantation criteria. The complete response (CR) + partial response (PR) rate for bortezomib alone was 30% [90% confidence interval (CI), 15.7-47.1] and 38% (90% CI, 22.6-56.4) in the 1.0 mg/m(2) (8 of 27 patients) and 1.3 mg/m(2) (10 of 26 patients) groups respectively. The CR + PR rate for patients who received bortezomib alone or in combination with dexamethasone was 37% and 50% for the 1.0 and 1.3 mg/m(2) cohorts respectively. The most common grade 3 adverse events were thrombocytopenia (24%), neutropenia (17%), lymphopenia (11%) and peripheral neuropathy (9%). Grade 4 events were observed in 9% (five of 54 patients). Bortezomib alone or in combination with dexamethasone demonstrated therapeutic activity in patients with multiple myeloma who relapsed after frontline therapy.
St. Vincent's Catholic Medical Center, New York, NY, USA. sjaganna@salick.com
S
S
Jagannath
B
B
Barlogie
J
J
Berenson
D
D
Siegel
D
D
Irwin
P G
PG
Richardson
R
R
Niesvizky
R
R
Alexanian
S A
SA
Limentani
M
M
Alsina
J
J
Adams
M
M
Kauffman
D-L
DL
Esseltine
D P
DP
Schenkein
K C
KC
Anderson
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001897:Boronic Acids / Q000008:administration & dosage* / Q000627:therapeutic use; D000069286:Bortezomib; D003907:Dexamethasone / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D011719:Pyrazines / Q000008:administration & dosage* / Q000627:therapeutic use; D012008:Recurrence; D015996:Survival Rate
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone