Retinoic acid and arsenic trioxide for acute promyelocytic leukemia.
By F. Lo‐Coco, G. Avvisati, M. Vignetti, C. Thiede, S. Orlando, S. Iacobelli, F. Ferrara, P. Fazi, L. Cicconi, E. di Bona and 38 more. New England Journal of Medicine, 2013
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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, ≤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%. 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.).
Subfields: Hematology, Molecular Biology, Public Health, Environmental and Occupational Health
View Paper: https://www.semanticscholar.org/paper/af4fa3804477715e27b764ac42fda080b8aea5a5
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Citations in the corpus
- Transcriptional Addiction in Cancer (2017, neutral): “Notably, innovation in clinical investigation would 9 ultimately pair ATRA with arsenic trioxide (also associated with PML-RARA degradation) in low- to intermediate-risk APML as effective first-line treatment, equivalent in efficacy to chemotherapy in this disease (Lo-Coco et al., 2013).”
- Acute myeloid leukemia: current progress and future directions (2021, background): “(9) Approaches to enhance T-cell immune responses to AML (as done in ALL) with T-cell engagers (BiTEs), checkpoint inhibitors, and chimeric antigen receptor (CAR)-T-cell approaches.”