TY - JOUR
T1 - A phase 2 study of Bortezomib in relapsed, refractory myeloma
AU - Richardson, Paul G.
AU - Barlogie, Bart
AU - Berenson, James
AU - Singhal, Seema
AU - Jagannath, Sundar
AU - Irwin, David
AU - Rajkumar, S. Vincent
AU - Srkalovic, Gordan
AU - Alsina, Melissa
AU - Alexanian, Raymond
AU - Siegel, David
AU - Orlowski, Robert Z.
AU - Kuter, David
AU - Limentani, Steven A.
AU - Lee, Stephanie
AU - Hideshima, Teru
AU - Esseltine, Dixie Lee
AU - Kauffman, Michael
AU - Adams, Julian
AU - Schenkein, David P.
AU - Anderson, Kenneth C.
PY - 2003/6/26
Y1 - 2003/6/26
N2 - BACKGROUND: Bortezomib, a boronic acid dipeptide, is a novel proteasome inhibitor that has been shown in preclinical and phase 1 studies to have antimyeloma activity. METHODS: In this multicenter, open-label, nonrandomized, phase 2 trial, we enrolled 202 patients with relapsed myeloma that was refractory to the therapy they had received most recently. Patients received 1.3 mg of bortezomib per square meter of body-surface area twice weekly for 2 weeks, followed by 1 week without treatment, for up to eight cycles (24 weeks). In patients with a suboptimal response, oral dexamethasone (20 mg daily, on the day of, and the day after bortezomib administration) was added to the regimen. The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee. RESULTS: Of 193 patients who could be evaluated, 92 percent had been treated with three or more of the major classes of agents for myeloma, and in 91 percent, the myeloma was refractory to the therapy received most recently. The rate of response to bortezomib was 35 percent, and those with a response included 7 patients in whom myeloma protein became undetectable and 12 in whom myeloma protein was detectable only by immunofixation. The median overall survival was 16 months, with a median duration of response of 12 months. Grade 3 adverse events included thrombocytopenia (in 28 percent of patients), fatigue (in 12 percent), peripheral neuropathy (in 12 percent), and neutropenia (in 11 percent). Grade 4 events occurred in 14 percent of patients. CONCLUSIONS: Bortezomib, a member of a new class of anticancer drugs, is active in patients with relapsed multiple myeloma that is refractory to conventional chemotherapy.
AB - BACKGROUND: Bortezomib, a boronic acid dipeptide, is a novel proteasome inhibitor that has been shown in preclinical and phase 1 studies to have antimyeloma activity. METHODS: In this multicenter, open-label, nonrandomized, phase 2 trial, we enrolled 202 patients with relapsed myeloma that was refractory to the therapy they had received most recently. Patients received 1.3 mg of bortezomib per square meter of body-surface area twice weekly for 2 weeks, followed by 1 week without treatment, for up to eight cycles (24 weeks). In patients with a suboptimal response, oral dexamethasone (20 mg daily, on the day of, and the day after bortezomib administration) was added to the regimen. The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee. RESULTS: Of 193 patients who could be evaluated, 92 percent had been treated with three or more of the major classes of agents for myeloma, and in 91 percent, the myeloma was refractory to the therapy received most recently. The rate of response to bortezomib was 35 percent, and those with a response included 7 patients in whom myeloma protein became undetectable and 12 in whom myeloma protein was detectable only by immunofixation. The median overall survival was 16 months, with a median duration of response of 12 months. Grade 3 adverse events included thrombocytopenia (in 28 percent of patients), fatigue (in 12 percent), peripheral neuropathy (in 12 percent), and neutropenia (in 11 percent). Grade 4 events occurred in 14 percent of patients. CONCLUSIONS: Bortezomib, a member of a new class of anticancer drugs, is active in patients with relapsed multiple myeloma that is refractory to conventional chemotherapy.
UR - http://www.scopus.com/inward/record.url?scp=0037973279&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037973279&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa030288
DO - 10.1056/NEJMoa030288
M3 - Article
C2 - 12826635
AN - SCOPUS:0037973279
SN - 0028-4793
VL - 348
SP - 2609
EP - 2617
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 26
ER -