Arsenic trioxide effective for newly diagnosed acute promyelocytic leukemia

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Arsenic trioxide is effective as single-agent therapy for newly diagnosed acute promyelocytic leukemia (APL), according to a report in the April 1 issue of Blood.

"It is possible to treat newly diagnosed APL with single agent arsenic," Dr. Vikram Mathews from Christian Medical College, Vellore, India told Reuters Health. "We do not believe that this will be the standard of care in the future, though in my country and others with limited resources it is probably the least expensive option to treat this condition."

Dr. Mathews and colleagues investigated the use of single-agent arsenic trioxide for remission induction, consolidation, and maintenance in the management of 72 newly diagnosed cases of APL.

Sixty-two (86.11%) of the 72 eligible patients achieved hematologic complete remission, the authors report. The other 10 patients died prior to achieving a complete remission.

Among the patients who achieved complete remission, 59 patients completed the consolidation and maintenance course. Forty-one patients who had attained molecular remission prior to the onset of consolidation remained in molecular remission at the end of consolidation, the results indicate. Eleven of the 12 patients who were positive prior to consolidation achieved molecular remission at the end of consolidation, and the remaining patient achieved molecular remission at the end of the first course of maintenance.

After remission induction, the researchers note, only four patients developed high-grade neutropenia, and only one patient developed febrile neutropenia that required hospitalization.

Non-hematologic toxicities in most patients were mild and frequently reverted during continued treatment, the report indicates. Significant hepatotoxicity developed in five patients, but in four cases it resolved with discontinuation of treatment and did not recur on rechallenge with arsenic trioxide.

Five patients (6.9%) developed definite differentiation syndrome or retinoic acid-like syndrome during induction, the investigators observe. However, there were no cases of differentiation syndrome during consolidation or maintenance phase.

At the time of analysis, 60 patients remain alive, 55 of them in first complete remission. All patients in first complete remission are also in molecular remission.

The three-year estimated overall survival is 86%, and the event-free survival and disease-free survival are 75% and 87%, respectively.

"Based on its efficacy and safety profile [arsenic trioxide] should be considered as an additional agent in upfront therapy for all newly diagnosed patients receiving 'conventional' regimens," Dr. Mathews said.

"Replacing standard chemotherapy with arsenic trioxide in newly diagnosed APL will require larger studies," writes Dr. Dan Douer from University Of Southern California Keck School of Medicine, Los Angeles, California in a related editorial. "However, for selected patients who cannot tolerate anthracycline-for example those with cardiac dysfunction, older adults with poor performance status, and possibly Jehovah's Witnesses, arsenic trioxide (probably still in combination with ATRA) would be a very reasonable alternative to the standard ATRA/chemotherapy."

"We are currently undertaking a multicenter trial in India to validate our single center experience," Dr. Mathews added. "We are also undertaking some basic science research activities at our institution to address mechanisms of resistance to arsenic in APL."