Randomized Phase III Study of Pegylated Liposomal Doxorubicin Plus Bortezomib Compared With Bortezomib Alone in Relapsed or Refractory Multiple Myeloma: Combination Therapy Improves Time to Progression
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Published:2007-09-01
Issue:25
Volume:25
Page:3892-3901
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ISSN:0732-183X
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Container-title:Journal of Clinical Oncology
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language:en
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Short-container-title:JCO
Author:
Orlowski Robert Z.1, Nagler Arnon1, Sonneveld Pieter1, Bladé Joan1, Hajek Roman1, Spencer Andrew1, San Miguel Jesús1, Robak Tadeusz1, Dmoszynska Anna1, Horvath Noemi1, Spicka Ivan1, Sutherland Heather J.1, Suvorov Alexander N.1, Zhuang Sen H.1, Parekh Trilok1, Xiu Liang1, Yuan Zhilong1, Rackoff Wayne1, Harousseau Jean-Luc1
Affiliation:
1. From the University of North Carolina at Chapel Hill, Chapel Hill, NC; Chaim Sheba Medical Center, Tel Hashomer, Israel; Erasmus MC, Rotterdam, the Netherlands; Hospital Clinic I Provincial, Barcelona, Spain; Interní Hematoonkologická klinika Fakultní Brno, Brno; General Faculty Hospital, Prague, Czech Republic; Alfred Hospital, Melbourne; Institute of Medicine and Veterinary Science, Adelaide, Australia; Hospital Universitario de Salamanca, Centro de Investigación del Cáncer- IBMCC (CSIC-USAL), Spain;...
Abstract
PurposeThis phase III international study compared the efficacy and safety of a combination of pegylated liposomal doxorubicin (PLD) plus bortezomib with bortezomib monotherapy in patients with relapsed or refractory multiple myeloma.Patients and MethodsSix hundred forty-six patients were randomly assigned to receive either intravenous bortezomib 1.3 mg/m2on days 1, 4, 8, and 11 of an every 21-days cycle, or the same bortezomib regimen with PLD 30 mg/m2on day 4.ResultsMedian time to progression was increased from 6.5 months for bortezomib to 9.3 months with the PLD + bortezomib combination (P = .000004; hazard ratio, 1.82 [monotherapy v combination therapy]; 95% CI, 1.41 to 2.35). The 15-month survival rate for PLD + bortezomib was 76% compared with 65% for bortezomib alone (P = .03). The complete plus partial response rate was 41% for bortezomib and 44% for PLD + bortezomib, a difference that was not statistically significant. Median duration of response was increased from 7.0 to 10.2 months (P = .0008) with PLD + bortezomib. Grade 3/4 adverse events were more frequent in the combination group (80% v 64%), with safety profiles consistent with the known toxicities of the two agents. An increased incidence in the combination group was seen of grade 3/4 neutropenia, thrombocytopenia, asthenia, fatigue, diarrhea, and hand-foot syndrome.ConclusionPLD with bortezomib is superior to bortezomib monotherapy for the treatment of patients with relapsed or refractory multiple myeloma. The combination therapy is associated with a higher incidence of grade 3/4 myelosuppression, constitutional symptoms, and GI and dermatologic toxicities.
Publisher
American Society of Clinical Oncology (ASCO)
Subject
Cancer Research,Oncology
Reference26 articles.
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