Arsenic trioxide boosts survival in leukemia

CHICAGO (Reuters Health) - In adults with newly diagnosed acute promyelocytic leukemia (APL), the addition of arsenic trioxide to standard therapy significantly improves survival, according to a phase III study presented over the weekend at the 43rd annual meeting of the American Society of Clinical Oncology.

APL is a cancer of the bone marrow that effects the production of white blood cells, which are essential for fighting off disease. This particular leukemia is characterized by a deficiency of mature myeloid cells and an excess of immature promyelocytes. This cancer is relatively rare and estimated to represent less than 10 percent of all leukemias.

The benefit of adding arsenic trioxide "occurs in all risk groups," lead investigator Dr. Bayard L. Powell of Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina reported. "The addition of arsenic trioxide adds very little in toxicity to standard consolidation therapy."

Arsenic trioxide is currently used as second-line therapy for APL patients who do not respond to standard therapy or who relapse after standard treatment. The current study, Powell said, suggests that "even more patients will benefit if we give it earlier in the course of treatment."

The differences in survival rates and relapse rates in their trial are "great enough to justify including arsenic trioxide in standard first-line treatment," Powell said.

The study enrolled 518 adults and 64 children older than 15 with untreated APL. Thirty-seven adults and 7 children were ineligible and were not included in the intention-to-treat analyses.

The subjects were randomly assigned to two 25-day courses of arsenic trioxide, in addition to standard therapy with all-trans retinoic acid, cytarabine and daunorubicin or to standard therapy only.

Patients who achieved remission progress to maintenance therapy with all-trans retinoic acid with or without 6-mercaptopurine and methotrexate for 1 year.

The overall the complete remission rate for adults was 89 percent and did not differ by treatment arm. Complete remission rate for children was also 89 percent.

However, after 3 years, the event-free survival was 77 percent in the arsenic treatment group compared with 59 percent in the standard treatment group. Overall survival was 86 percent in the arsenic arm compared with 77 percent in the standard group. Survival for pediatric patients did not differ statistically from that of adults not given arsenic trioxide.

Based on this study, Powell concluded that "arsenic trioxide should be incorporated into the therapy of patients with untreated APL."