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Blood, 5 November 2009, Vol. 114, No. 19, pp. 4027-4033. Prepublished online as a Blood First Edition Paper on August 26, 2009; DOI 10.1182/blood-2009-06-229351. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2009-06-229351v1 114/19/4027    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Giles, F. Articles by O'Brien, S. PubMed PubMed Citation Articles by Giles, F. Articles by O'Brien, S. Related Collections Free Research Articles Myeloid Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Phase 3 randomized, placebo-controlled, double-blind study of high-dose continuous infusion cytarabine alone or with laromustine (VNP40101M) in patients with acute myeloid leukemia in first relapse Francis Giles1, Norbert Vey2, Daniel DeAngelo3, Karen Seiter4, Wendy Stock5, Robert Stuart6, Darinka Boskovic7, Arnaud Pigneux8, Martin Tallman9, Joseph Brandwein10, Jonathan Kell11, Tadeusz Robak12, Peter Staib13, Xavier Thomas14, Ann Cahill15, Maher Albitar16, and Susan O'Brien17 1 Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center, San Antonio; 2 Institut Paoli Calmettes, Marseille, France; 3 Dana-Farber Cancer Institute, Boston, MA; 4 New York Medical College, Valhalla; 5 University of Chicago, IL; 6 Medical University of South Carolina (MUSC) Hollings Cancer Center, Charleston; 7 Clinical Center of Serbia, Belgrade, Serbia; 8 Hôpital Haut Lévèque, Bordeaux, France; 9 Robert H. Lurie Comprehensive Cancer Center, Chicago, IL; 10 Princess Margaret Hospital, Toronto, ON; 11 University Hospital of Wales, Cardiff, United Kingdom; 12 Medical University of Lodz, Lodz, Poland; 13 Klinikum der Universität Köln, Köln, Germany; 14 Hôpital Edouard Herriot, Lyon, France; 15 Vion Pharmaceuticals, New Haven, CT; 16 Quest Diagnostics Nichols Institute, San Juan Capistrano, CA; and 17 University of Texas (UT) M. D. Anderson Cancer Center, Houston Laromustine is a sulfonylhdrazine alkylator with significant antileukemia activity. An international, randomized (2:1), double-blind, placebo-controlled study was conducted to compare complete remission (CR) rates and overall survival (OS) in patients with first relapse acute myeloid leukemia (AML) treated with laromustine and high-dose cytarabine (HDAC) versus HDAC/placebo. Patients received 1.5 g/m2 per day cytarabine continuous infusion for 3 days and laromustine 600 mg/m2 (n = 177) or placebo (n = 86) on day 2. Patients in CR received consolidation with laromustine/HDAC or HDAC/placebo as per initial randomization. After interim analysis at 50% enrollment, the Data Safety Monitoring Board (DSMB) expressed concern that any advantage in CR would be compromised by the observed on-study mortality, and enrollment was held. The CR rate was significantly higher for the laromustine/HDAC group (35% vs 19%, P = .005). However, the 30-day mortality rate and median progression-free survival were significantly worse in this group compared with HDAC/placebo (11% vs 2%; P = .016; 54 days vs 34; P = .002). OS and median response durations were similar in both groups. Laromustine/HDAC induced significantly more CR than HDAC/placebo, but OS was not improved due to mortality associated with myelosuppression and its sequelae. The DSMB subsequently approved a revised protocol with laromustine dose reduction and recombinant growth factor support. The study was registered as NCT00112554 [ClinicalTrials.gov] at http://www.clinicaltrials.gov. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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