Randomized Phase III Trial of Retinoic Acid and Arsenic Trioxide Versus Retinoic Acid and Chemotherapy in Patients With Acute Promyelocytic Leukemia: Health-Related Quality-of-Life Outcomes Fabio Efficace, Franco Mandelli, Giuseppe Avvisati, Francesco Cottone, Felicetto Ferrara, Eros Di Bona, Giorgina Specchia, Massimo Breccia, Alessandro Levis, Simona Sica, Olimpia Finizio, Maria Grazia Kropp, Giuseppe Fioritoni, Elisa Cerqui, Marco Vignetti, Sergio Amadori, Richard F. Schlenk, Uwe Platzbecker, and Francesco Lo-Coco Fabio Efficace, Franco Mandelli, Francesco Cottone, and Marco Vignetti, Gruppo Ital- iano Malattie Ematologiche dell’Adulto; Giuseppe Avvisati, Universita ` Campus Biomedico; Massimo Breccia, Universita ` “La Sapienza,”; Simona Sica, Universita ` Cattolica Sacro Cuore; Sergio Amadori and Francesco Lo-Coco, Universita ` Tor Vergata; Francesco Lo-Coco, Fondazione Santa Lucia, Roma; Felicetto Ferrara, Ospedale Cardarelli; Olimpia Finizio, Ospedale Cardarelli, Napoli; Eros Di Bona, Ospedale San Bortolo, Vicenza; Giorgina Specchia, Universita ` di Bari, Bari; Alessandro Levis, Ospedale SS Antonio e Biagio, Alessandria; Maria Grazia Kropp, Azienda Ospedaliera Pugliese Ciaccio, Catanzaro; Giuseppe Fiori- toni, Ospedale Civile, Pescara; Elisa Cerqui, Spedali Civili, Brescia, Italy; Richard F. Schlenk, University of Ulm, Ulm; and Uwe Platzbecker, Universitatsklinikum Carl Gustav Carus, Dresden, Germany. Published online ahead of print at www.jco.org on September 22, 2014. Supported in Italy by the Associazione Itali- ana contro le Leucemie-linfomi e mieloma and Associazione Italiana per la Ricerca sul Cancro (Grant No. IG 5916 to F.L.-C.); in Germany by the Federal Ministry of Educa- tion and Research (Grant No. BMBF FKZ 01KG0903 to U.P.); and in part by Lund- beck (Montreal, Quebec, Canada). Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org. Presented at the 19th Congress of the European Hematology Association, Milan, Italy, June 12-15, 2014. Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article. Clinical trial information: NCT00482833. Corresponding author: Fabio Efficace, PhD, Health Outcomes Research Unit, Italian Group for Adult Hematologic Diseases (GIMEMA), GIMEMA Data Center, Via Benevento 6, 00161, Rome, Italy; e-mail: f.efficace@gimema.it. © 2014 by American Society of Clinical Oncology 0732-183X/14/3230w-3406w/$20.00 DOI: 10.1200/JCO.2014.55.3453 A B S T R A C T Purpose A randomized clinical trial compared efficacy and toxicity of standard all-trans-retinoic acid (ATRA) plus chemotherapy versus ATRA plus arsenic trioxide in patients with newly diagnosed, low- or intermediate-risk acute promyelocytic leukemia (APL). Here, we report health-related quality-of-life (HRQOL) results. Patients and Methods HRQOL was a secondary end point of this trial. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 was used to assess HRQOL at end of induction and after consolidation therapy. All analyses were based on 156 patients who received at least one dose of treatment, with groups defined according to randomly assigned treatment. Primary analysis was performed, estimating mean HRQOL score over time and differences between treatment arms using a linear mixed model. Results Overall, 162 patients age 18 to 70 years were enrolled. Of these, 150 and 142 patients were evaluable for HRQOL after induction therapy and third consolidation course, respectively. Overall compliance with HRQOL forms was 80.1%. The largest difference, favoring patients treated with ATRA plus arsenic trioxide, was found for fatigue severity (mean score difference, -9.3; 95% CI, -17.8 to -0.7; P = .034) at end of induction therapy. This difference was also clinically relevant. HRQOL differences between treatment arms at end of consolidation showed that for several scales, differences between treatment arms were marginal. Conclusion Overall, current HRQOL findings further support the use of ATRA plus arsenic trioxide as preferred first-line treatment in patients with low- or intermediate-risk APL. J Clin Oncol 32:3406-3412. © 2014 by American Society of Clinical Oncology INTRODUCTION Acute promyelocytic leukemia (APL) is a special subtype of acute myeloid leukemia (AML) charac- terized by leukemic bone marrow infiltration by dysplastic promyelocytes, a specific chromosomal translocation [t(15;17)], and life-threatening coagu- lopathy. 1 With the advent of modern treatment with all- trans -retinoic acid (ATRA) and anthracycline- based chemotherapy, APL has become a highly curable disease, with long-term survival rates exceeding 75% as reported by several large multicenter trials. Thus, ATRA plus chemotherapy has been regarded until re- cently as the standard therapy for these patients. 1,2 On the basis of earlier findings showing that arsenic trioxide, with or without ATRA, was also highly effective in APL and associated with a better safety profile, 3-5 we recently carried out a phase III randomized clinical trial (RCT) to compare efficacy and toxicity of standard ATRA plus chemotherapy versus ATRA plus arsenic tri- oxide in patients with newly diagnosed APL. 6 This RCT, conducted by the Gruppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA), the German-Austrian Acute Myeloid Leukemia Study Group (AMLSG), and Study Alliance Leu- kemia (SAL), showed that ATRA plus arsenic tri- oxide was at least not inferior to ATRA plus JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 32  NUMBER 30  OCTOBER 20 2014 3406 © 2014 by American Society of Clinical Oncology Downloaded from jco.ascopubs.org on July 22, 2016. For personal use only. 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