Ovid: Welcome to Ovid

Retinoic Acid and Arsenic Trioxide for Acute Promyelocytic Leukemia.
Lo-Coco, Francesco M.D.; Avvisati, Giuseppe M.D., Ph.D.; Vignetti, Marco M.D.; Thiede, Christian M.D.; Orlando, Sonia Maria B.Sc.; Iacobelli, Simona Ph.D.; Ferrara, Felicetto M.D.; Fazi, Paola M.D.; Cicconi, Laura M.D.; Di Bona, Eros M.D.; Specchia, Giorgina M.D.; Sica, Simona M.D.; Divona, Mariadomenica B.Sc.; Levis, Alessandro M.D.; Fiedler, Walter M.D.; Cerqui, Elisa M.D.; Breccia, Massimo M.D.; Fioritoni, Giuseppe M.D.; Salih, Helmut R. M.D.; Cazzola, Mario M.D.; Melillo, Lorella M.D.; Carella, Angelo M. M.D.; Brandts, Christian H. M.D.; Morra, Enrica M.D.; von Lilienfeld-Toal, Marie M.D.; Hertenstein, Bernd M.D.; Wattad, Mohammed M.D.; Lubbert, Michael M.D.; Hanel, Matthias M.D.; Schmitz, Norbert M.D.; Link, Hartmut M.D.; Kropp, Maria Grazia M.D.; Rambaldi, Alessandro M.D.; La Nasa, Giorgio M.D.; Luppi, Mario M.D.; Ciceri, Fabio M.D.; Finizio, Olimpia M.D.; Venditti, Adriano M.D.; Fabbiano, Francesco M.D.; Dohner, Konstanze M.D.; Sauer, Michaela B.Sc.; Ganser, Arnold M.D.; Amadori, Sergio M.D.; Mandelli, Franco M.D.; Dohner, Hartmut M.D.; Ehninger, Gerhard M.D.; Schlenk, Richard F. M.D.; Platzbecker, Uwe M.D.; Gruppo Italiano Malattie Ematologiche dell'Adulto, the German-Austrian Acute Myeloid Leukemia Study Group, and Study Alliance Leukemia
[Article] New England Journal of Medicine. 369(2):111-121, July 11, 2013.

(Format: HTML, PDF)

BACKGROUND: All-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.

METHODS: We 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, <=10x109 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%.

RESULTS: Complete 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.

CONCLUSIONS: ATRA 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.)