• Francesco Lo-Coco, Giuseppe Avvisati, Marco Vignetti, Christian Thiede, Sonia Maria Orlando, Simona Iacobelli, Felicetto Ferrara, Paola Fazi, Laura Cicconi, Eros Di Bona, Giorgina Specchia, Simona Sica, Mariadomenica Divona, Alessandro Levis, Walter Fiedler, Elisa Cerqui, Massimo Breccia, Giuseppe Fioritoni, Helmut R Salih, Mario Cazzola, Lorella Melillo, Angelo M Carella, Christian H Brandts, Enrica Morra, Marie von Lilienfeld-Toal, Bernd Hertenstein, Mohammed Wattad, Michael Lübbert, Matthias Hänel, Norbert Schmitz, Hartmut Link, Maria Grazia Kropp, Alessandro Rambaldi, Giorgio La Nasa, Mario Luppi, Fabio Ciceri, Olimpia Finizio, Adriano Venditti, Francesco Fabbiano, Konstanze Döhner, Michaela Sauer, Arnold Ganser, Sergio Amadori, Franco Mandelli, Hartmut Döhner, Gerhard Ehninger, Richard F Schlenk, Uwe Platzbecker, Gruppo Italiano Malattie Ematologiche dell'Adulto, German-Austrian Acute Myeloid Leukemia Study Group, and Study Alliance Leukemia.
• Dipartimento di Biomedicina e Prevenzione, Università Tor Vergata, Rome, Italy. francesco.lo.coco@uniroma2.it
• N. Engl. J. Med.. 2013 Jul 11;369(2):111-21.

BackgroundAll-trans retinoic acid (ATRA) with chemotherapy is the standard of care for acute promyelocytic leukemia (APL), resulting in cure rates exceeding 80%. Pilot studies of treatment with arsenic trioxide with or without ATRA have shown high efficacy and reduced hematologic toxicity.MethodsWe conducted a phase 3, multicenter trial comparing ATRA plus chemotherapy with ATRA plus arsenic trioxide in patients with APL classified as low-to-intermediate risk (white-cell count, ≤10×10(9) per liter). Patients were randomly assigned to receive either ATRA plus arsenic trioxide for induction and consolidation therapy or standard ATRA-idarubicin induction therapy followed by three cycles of consolidation therapy with ATRA plus chemotherapy and maintenance therapy with low-dose chemotherapy and ATRA. The study was designed as a noninferiority trial to show that the difference between the rates of event-free survival at 2 years in the two groups was not greater than 5%.ResultsComplete remission was achieved in all 77 patients in the ATRA-arsenic trioxide group who could be evaluated (100%) and in 75 of 79 patients in the ATRA-chemotherapy group (95%) (P=0.12). The median follow-up was 34.4 months. Two-year event-free survival rates were 97% in the ATRA-arsenic trioxide group and 86% in the ATRA-chemotherapy group (95% confidence interval for the difference, 2 to 22 percentage points; P<0.001 for noninferiority and P=0.02 for superiority of ATRA-arsenic trioxide). Overall survival was also better with ATRA-arsenic trioxide (P=0.02). As compared with ATRA-chemotherapy, ATRA-arsenic trioxide was associated with less hematologic toxicity and fewer infections but with more hepatic toxicity.ConclusionsATRA plus arsenic trioxide is at least not inferior and may be superior to ATRA plus chemotherapy in the treatment of patients with low-to-intermediate-risk APL. (Funded by Associazione Italiana contro le Leucemie and others; ClinicalTrials.gov number, NCT00482833.).

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