Researchers from India have reported that single-agent arsenic trioxide (ATO), without ATRA (all-trans retinoic acid) and combination chemotherapy, results in an event-free survival of 75% in patients with acute promyelocytic leukemia (APL). The details of this phase II study were reported in the April 1, 2006 issue of Blood.[1]

Patients with APL have (T15:17). This subset represents 10%-15% of all cases of acute myeloid leukemia (AML). Standard treatment is ATRA plus an anthracycline for induction, and 2 years of ATRA and low-dose chemotherapy for maintenance; this results in an 80% DFS. Arsenic trioxide is the best reported chemotherapy salvage therapy for patients with APL who relapse following an initial remission. The CR rate is essentially 100%, and the long-term disease-free survival is 85% following salvage therapy with ATO.

In a recent study, researchers replaced an anthracycline in the induction regimen with ATO. They randomly allocated 61 patients with newly diagnosed APL to receive ATRA alone, ATO alone, or the combination of ATRA and ATO. Consolidation in all arms was doxorubicin, cytarabine, and homoharrington administered sequentially followed by ATRA maintenance. One patient in the ATRA arm died of treatment-related complications and 90% to 100% of all patients, irrespective of assignment, achieved a CR. Patients in the combination arm had more rapid production of PCR-negative state than either of the monotherapy arms. This difference persisted through consolidation. Relapses occurred in 20% of the ATRA arm, 10% of the arsenic trioxide arm, and in none on the combination arm. The authors suggested that this study demonstrated synergy between ATRA and arsenic trioxide with more rapid and more complete disappearance of tumor as measured by real time PCR.

The current study evaluated ATO alone as therapy for 72 patients with newly diagnosed APL. However, 74% of patients received hydroxyurea to lower elevated blood counts, and eight patients also received an anathracycline. Arsenic trioxide was administered for induction, consolidation, and maintenance in this study. The median follow-up was 2 years. The complete remission rate was 86%. One patient died in remission and only six have relapsed. Event-free survival at 3 years was 75%. The relapse rate was 12%. Overall survival was 86%. All 55 patients in first complete remission are in molecular complete remission by PCR. Toxicity of the regimen was described as minimal, and most therapy after initial disease control was administered in an outpatient setting. The authors also pointed out that this therapy is relatively inexpensive compared to standard treatment for APL with combination chemotherapy and ATRA.

Comments: These are interesting results and at least as good as observed with chemotherapy and ATRA. An accompanying editorial suggests that larger studies will be needed before single-agent ATO replaces chemotherapy and ATRA as standard treatment for APL.[2] It would, however, appear that ATO should be incorporated into initial therapy of APL.

Related News:

LongTerm Follow-up Confirms Importance of ATRA in Curing Acute Promyelocytic Leukemia (12/5/2002)

Cytogenetic Classification of Acute Myeloid Leukemia Outlined (12/5/2002)

Arsenic Trioxide is Best Therapy for Relapsed Acute Promyelocytic Leukemia (4/24/2003)

Arsenic Trioxide and ATRA Highly Effective for Remission Induction of APL (12/12/2003)

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