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Lo-Coco 2013

"ATRA plus Arsenic Trioxide for Acute Promyelocytic Leukemia".The New England Journal of Medicine. 2013. 369:111-121.

Links to original sources: Wiki Journal Post Full Journal Article

Contents

1 Clinical Question 2 Bottom Line 3 Major Points 4 Guidelines 5 Design 6 Population 6.1 Inclusion Criteria 6.2 Exclusion Criteria 6.3 Baseline Characteristics 7 Interventions 8 Outcomes 8.1 Primary Outcome 8.2 Secondary Outcomes 9 Funding 10 Further Reading

Clinical Question


Is ATRA plus arsenic trioxide as effective as the standard ATRA plus chemotherapy for the treatment of patients with low-to-intermediate-risk acute promyelocytic leukemia?

Bottom Line


For patients with low-to-intermediate-risk acute promyelocytic leukemia, ATRA plus arsenic trioxide is at least not inferior and may be superior to ATRA plus chemotherapy in terms of event-free survival and overall survival, with reduced hematologic toxicity but more hepatic toxicity.

Major Points


Acute promyelocytic leukemia (APL) has become highly curable with the standard treatment of ATRA and chemotherapy, but pilot studies suggested that arsenic trioxide with or without ATRA may lead to reduced hematologic toxicity and high efficacy.

Guidelines


There are no specific guidelines recommending ATRA plus arsenic trioxide over standard chemotherapy regimens based on this study alone as the knowledge cutoff for this summary does not include any guidelines published after this study.

Design


Prospective, randomized, multicenter, open-label, phase 3 noninferiority trial comparing ATRA-arsenic trioxide with standard ATRA-chemotherapy.

Population


Patients aged 18 to 71 years with newly diagnosed, low-to-intermediate-risk APL (white-cell count, ≤10×10^9 per liter).

Inclusion Criteria

- Newly diagnosed APL classified as low-to-intermediate risk (white-cell count at diagnosis, ≤10×10^9 per liter) - Confirmed genetic diagnosis of PML-RARA fusion gene by RT-PCR, t(15;17) translocation, or microspeckled PML pattern by immunofluorescence - Aged 18 to 71 years

Exclusion Criteria

- High-risk APL - White-cell count greater than 10×10^9 per liter

Baseline Characteristics

- Comparable demographic, clinical, and biologic characteristics between the two treatment cohorts

Interventions


Patients were randomized to receive ATRA plus arsenic trioxide for induction and consolidation therapy or standard ATRA-chemotherapy for induction, followed by consolidation and maintenance therapy with chemotherapy and ATRA.

Outcomes


Primary Outcome

- Event-free survival at 2 years with fewer failures (no remissions, relapses, or deaths) in the ATRA-arsenic trioxide group compared to the ATRA-chemotherapy group.

Outcomes


- Higher overall survival in the ATRA-arsenic trioxide group - Similar antileukemic efficacy - More hepatic toxicity but less hematologic toxicity and fewer infections in ATRA-arsenic trioxide group

Funding


- Funded by Associazione Italiana contro le Leucemie and others

Further Reading


- The study is published in The New England Journal of Medicine, DOI: 10.1056/NEJMoa1300874 - ClinicalTrials.gov number, NCT00482833