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ATRA-Arsenic Trioxide May be Superior to Standard ATRA-Chemotherapy for Acute Promyelocytic Leukemia

The treatment combination consisting of all-trans retinoic acid (ATRA) plus arsenic trioxide appears superior to the standard ATRA plus chemotherapy for acute promyelocytic leukemia (APL). These results were recently published in the New England Journal of Medicine.

Acute promyelocytic leukemia is actually considered to be a subset of acute myeloid leukemia. It is a fairly aggressive type of leukemia, with a younger median age of diagnosis than most other leukemias.

Fortunately, APL responds well to standard therapies and cure rates are high.

One standard agent used in the treatment of APL is ATRA, a derivative of vitamin A. APL has demonstrated high anti-cancer responses to ATRA, which is typically coupled with a chemotherapy regimen.

The chemotherapy given with ATRA is unfortunately associated with side effects, which can be life-threatening and/or last for quite some time. Therefore, researchers are constantly searching for ways in which to maintain cure rates but reduce side effects of therapy.

Researchers from Europe associated with the Gruppo Italiano Malattie Ematologiche dell’Adulto, the German–Austrian Acute Myeloid Leukemia Study Group, and Study Alliance Leukemia recently conducted a phase III clinical trial to directly compare ATRA plus chemotherapy to ATRA plus arsenic trioxide in patients with APL. The trial consisted of 156 patients with low- to intermediate-risk APL. Approximately half received ATRA/chemotherapy and the other half received ATRA/arsenic trioxide.

Complete remissions occurred in 100% of patients treated with ATRA/arsenic trioxide, and 95% of patients treated with ATRA/chemotherapy.
At approximately 34 months, survival rates were 97% for those treated with ATRA/arsenic trioxide and 86% for those treated with ATRA/chemotherapy.
ATRA/arsenic trioxide resulted in fewer side effects in regards to low blood cell levels and infections than ATRA/chemotherapy; however, ATRA/arsenic trioxide resulted in more side effects associated with the liver.
The authors stated that ATRA plus arsenic trioxide “may be superior to ATRA plus chemotherapy in the treatment of patients with low-to-intermediate-risk APL. Patients with APL may wish to speak with their healthcare provider regarding their own risks and benefits of treatment with ATRA plus arsenic trioxide versus the standard ATRA plus chemotherapy regimen.

Reference: Lo-Coco F, Avvisati G, Vignetti M, et al. Retinoic Acid and Arsenic Trioxide for Acute Promyelocytic Leukemia. New England Journal of Medicine. 2013; 369:111-121.