TY - JOUR
T1 - A randomized phase 2 trial of a preparative regimen of bortezomib, high-dose melphalan, arsenic trioxide, and ascorbic acid
AU - Sharma, Manish
AU - Khan, Hassan
AU - Thall, Peter F.
AU - Orlowski, Robert Z.
AU - Bassett, Roland L.
AU - Shah, Nina
AU - Bashir, Qaiser
AU - Parmar, Simrit
AU - Wang, Michael
AU - Shah, Jatin J.
AU - Hosing, Chitra M.
AU - Popat, Uday R.
AU - Giralt, Sergio A.
AU - Champlin, Richard E.
AU - Qazilbash, Muzaffar H.
PY - 2012/5/1
Y1 - 2012/5/1
N2 - BACKGROUND: Bortezomib is active for newly diagnosed and relapsed multiple myeloma, and it has synergistic activity with melphalan. The authors of this report conducted a randomized trial to determine the safety and efficacy of adding bortezomib to a preparative regimen of arsenic trioxide (ATO), ascorbic acid (AA), and melphalan. METHODS: Among 60 patients who enrolled between October 2006 and September 2007, 58 patients underwent autologous transplantation with a preparative regimen of melphalan 200 mg/m 2 intravenously, AA 1000 mg daily intravenously for 7 days, and ATO 0.25 mg/kg intravenously for 7 days. Patients were randomized to receive no bortezomib (Group 1), bortezomib 1 mg/m 2 × 3 doses (Group 2), and bortezomib 1.5 mg/m 2 × 3 doses (Group 3). Primary endpoints were complete response (CR), grade IV toxicity, and 90-day treatment-related mortality (TRM). Secondary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: The median follow-up of all surviving patients was 36 months (range, 20-43 months). The CR rates in Groups 1, 2, and 3 were 20%, 10%, and 10%, respectively. Grade 3 and 4 nonhematologic toxicities and TRM were comparable. The median OS was not reached in the groups, whereas the median PFS in Groups 1, 2, and 3 was 17.8 months, 17.4 months, and 20.7 months, respectively. PFS and OS were significantly shorter in patients who had high-risk cytogenetics (P =.016 and P =.0001, respectively) and relapsed disease (P =.0001 and P =.0001, respectively) regardless of the treatment group. CONCLUSIONS: Adding bortezomib to a preparative regimen of ATO, AA, and high-dose melphalan was safe and well tolerated in patients with multiple myeloma. There was no significant improvement in the CR rate, PFS, or OS in the bortezomib groups.
AB - BACKGROUND: Bortezomib is active for newly diagnosed and relapsed multiple myeloma, and it has synergistic activity with melphalan. The authors of this report conducted a randomized trial to determine the safety and efficacy of adding bortezomib to a preparative regimen of arsenic trioxide (ATO), ascorbic acid (AA), and melphalan. METHODS: Among 60 patients who enrolled between October 2006 and September 2007, 58 patients underwent autologous transplantation with a preparative regimen of melphalan 200 mg/m 2 intravenously, AA 1000 mg daily intravenously for 7 days, and ATO 0.25 mg/kg intravenously for 7 days. Patients were randomized to receive no bortezomib (Group 1), bortezomib 1 mg/m 2 × 3 doses (Group 2), and bortezomib 1.5 mg/m 2 × 3 doses (Group 3). Primary endpoints were complete response (CR), grade IV toxicity, and 90-day treatment-related mortality (TRM). Secondary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: The median follow-up of all surviving patients was 36 months (range, 20-43 months). The CR rates in Groups 1, 2, and 3 were 20%, 10%, and 10%, respectively. Grade 3 and 4 nonhematologic toxicities and TRM were comparable. The median OS was not reached in the groups, whereas the median PFS in Groups 1, 2, and 3 was 17.8 months, 17.4 months, and 20.7 months, respectively. PFS and OS were significantly shorter in patients who had high-risk cytogenetics (P =.016 and P =.0001, respectively) and relapsed disease (P =.0001 and P =.0001, respectively) regardless of the treatment group. CONCLUSIONS: Adding bortezomib to a preparative regimen of ATO, AA, and high-dose melphalan was safe and well tolerated in patients with multiple myeloma. There was no significant improvement in the CR rate, PFS, or OS in the bortezomib groups.
KW - arsenic trioxide
KW - autologous transplantation
KW - bortezomib
KW - melphalan
KW - myeloma
UR - http://www.scopus.com/inward/record.url?scp=84860219808&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860219808&partnerID=8YFLogxK
U2 - 10.1002/cncr.26517
DO - 10.1002/cncr.26517
M3 - Article
C2 - 21887685
AN - SCOPUS:84860219808
SN - 0008-543X
VL - 118
SP - 2507
EP - 2515
JO - Cancer
JF - Cancer
IS - 9
ER -