Treatment combining arsenic trioxide with standard care for acute promyelocytic leukemia (APL) was just as effective as conventional therapy in low-to-intermediate risk disease, and may even be superior, a recent study indicates.

All-trans retinoic acid (ATRA) with chemotherapy is the standard of care for APL, a subtype of acute myeloid leukemia (AML). This treatment yields cure rates exceeding 80%, noted Francesco Lo-Coco, MD, of the Department of Biomedicine and Prevention at the University Tor Vergata in Rome, Italy, and colleagues in their report for The New England Journal of Medicine (2013;369:111-121).

Acknowledging that pilot studies of treatment with arsenic trioxide with or without ATRA have shown high efficacy and reduced hematologic toxicity, Lo-Coco’s and colleagues conducted a phase 3, multicenter trial to compare ATRA plus chemotherapy with ATRA plus arsenic trioxide in persons with APL classified as low-to-intermediate risk (white cell count ≤10 x 109 per liter). As the authors explained, the study was designed as a “noninferiority trial” to show that the difference between the rates of event-free survival at two years in the two groups was not greater than 5%.

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Patients were randomized to receive either ATRA plus arsenic trioxide for induction and consolidation therapy or standard ATRA-idarubicin induction therapy followed by three cycles of consolidation with ATRA plus chemotherapy and maintenance therapy with low-dose chemotherapy and ATRA.

All 77 patients in the ATRA–arsenic trioxide group achieved complete remission, as did 75 of 79 evaluable patients (95%) in the ATRA-chemotherapy group. 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 other group. Overall survival was also better with ATRA–arsenic trioxide.

In addition, ATRA–arsenic trioxide therapy was associated with less hematologic toxicity and fewer infections, but with more hepatic toxicity, than was ATRA plus chemotherapy.