High-Dose Vincristine Sulfate Liposome Injection for Advanced, Relapsed, and Refractory Adult Philadelphia Chromosome–Negative Acute Lymphoblastic Leukemia
-
Published:2013-02-20
Issue:6
Volume:31
Page:676-683
-
ISSN:0732-183X
-
Container-title:Journal of Clinical Oncology
-
language:en
-
Short-container-title:JCO
Author:
O'Brien Susan1, Schiller Gary1, Lister John1, Damon Lloyd1, Goldberg Stuart1, Aulitzky Walter1, Ben-Yehuda Dina1, Stock Wendy1, Coutre Steven1, Douer Dan1, Heffner Leonard T.1, Larson Melissa1, Seiter Karen1, Smith Scott1, Assouline Sarit1, Kuriakose Philip1, Maness Lori1, Nagler Arnon1, Rowe Jacob1, Schaich Markus1, Shpilberg Ofer1, Yee Karen1, Schmieder Guenter1, Silverman Jeffrey A.1, Thomas Deborah1, Deitcher Steven R.1, Kantarjian Hagop1
Affiliation:
1. Susan O'Brien, Deborah Thomas, Hagop Kantarjian, University of Texas, MD Anderson Cancer Center, Houston, TX; Gary Schiller, University of California Los Angeles Medical Center; Dan Douer, University of Southern California Medical Center, Los Angeles; University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco; Stanford University School of Medicine, Stanford; Jeffrey A. Silverman, Steven R. Deitcher, Talon Therapeutics, San Mateo, CA; John Lister, Western...
Abstract
Purpose Relapsed adult acute lymphoblastic leukemia (ALL) is associated with high reinduction mortality, chemotherapy resistance, and rapid progression leading to death. Vincristine sulfate liposome injection (VSLI), sphingomyelin and cholesterol nanoparticle vincristine (VCR), facilitates VCR dose-intensification and densification plus enhances target tissue delivery. We evaluated high-dose VSLI monotherapy in adults with Philadelphia chromosome (Ph) –negative ALL that was multiply relapsed, relapsed and refractory to reinduction, and/or relapsed after hematopoietic cell transplantation (HCT). Patients and Methods Sixty-five adults with Ph-negative ALL in second or greater relapse or whose disease had progressed following two or more leukemia therapies were treated in this pivotal phase II, multinational trial. Intravenous VSLI 2.25 mg/m2, without dose capping, was administered once per week until response, progression, toxicity, or pursuit of HCT. The primary end point was achievement of complete response (CR) or CR with incomplete hematologic recovery (CRi). Results The CR/CRi rate was 20% and overall response rate was 35%. VSLI monotherapy was effective as third-, fourth-, and fifth-line therapy and in patients refractory to other single- and multiagent reinduction therapies. Median CR/CRi duration was 23 weeks (range, 5 to 66 weeks); 12 patients bridged to a post-VSLI HCT, and five patients were long-term survivors. VSLI was generally well tolerated and associated with a low 30-day mortality rate (12%). Conclusion High-dose VSLI monotherapy resulted in meaningful clinical outcomes including durable responses and bridging to HCT in advanced ALL settings. The toxicity profile of VSLI was predictable, manageable, and comparable to standard VCR despite the delivery of large, normally unachievable, individual and cumulative doses of VCR.
Publisher
American Society of Clinical Oncology (ASCO)
Subject
Cancer Research,Oncology
Cited by
158 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|