Arsenic Compound Improves Survival in Acute Promyelocytic Leukemia Patients

Publication
Article
OncologyONCOLOGY Vol 21 No 10
Volume 21
Issue 10

A study presented at the 2007 annual meeting of the American Society of Clinical Oncology (ASCO) has found that the addition of arsenic trioxide (Trisenox) to standard therapy significantly increases survival among adult patients with newly diagnosed acute promyelocytic leukemia (APL).

A study presented at the 2007 annual meeting of the American Society of Clinical Oncology (ASCO) has found that the addition of arsenic trioxide (Trisenox) to standard therapy significantly increases survival among adult patients with newly diagnosed acute promyelocytic leukemia (APL). Previously, arsenic trioxide was used as second-line treatment for patients who do not respond to standard therapy.

APL, a subtype of acute myeloid leukemia (AML), accounts for approximately 10% of AML cases, or about 1,500 cases per year in the United States. It is most often diagnosed in young and middle-aged adults. Arsenic has historically been known as a potent poison, but its use in traditional Chinese medicine led to its development as a treatment for leukemia.

Trial Results

Standard treatment for APL involves three stages of treatment—induction, consolidation, and maintenance therapy. In this multi-institutional phase III trial, 237 adults were randomized to receive standard consolidation therapy and 243 adults were randomized to receive two courses of arsenic trioxide in addition to the standard consolidation treatment. An additional 57 pediatric patients (age < 15 years) were not randomized and received standard treatment. Patients participated through one of five National Cancer Institute-sponsored North American Cooperative Oncology Groups.

After 3 years, overall survival was 86% in the arsenic trioxide arm (as well as in the pediatric group) vs 79% in the standard treatment arm (P = .0346). Event-free survival was 81% in the arsenic trioxide arm compared with 66% in the standard arm (P = .0011) Event-free survival in the pediatric group was 62%, not significantly different from that in adults who did not receive arsenic trioxide.

Cardiac irregularities and blood-related side effects such as low blood counts were not significantly different in the two arms. Other side effects, including infections and headaches, were higher in the arsenic trioxide arm (43% vs 28%).

"The differences in survival rates and relapse rates are great enough to justify including arsenic trioxide in standard first-line treatment," said Dr. Bayard L. Powell, professor of hematology and oncology at Wake Forest University Baptist Medical Center, Winston-Salem, NC, and the study's lead author. "Arsenic trioxide has already shown great benefits as a second-line treatment for APL, a cancer for which patients previously had few good treatment options. This study shows that even more patients will benefit if we give it earlier in the course of treatment."

Analysis by Risk Group

The examination of outcomes by risk groups showed that complete remission rates, death during induction, and early relapses at 1 year were all very similar for low-and intermediate-risk patients, but all three outcomes were significantly inferior for patients in the high-risk group (defined by white blood cell counts > 10,000/µL). High-risk patients treated with arsenic experienced a substantial number of early events during induction, "but once patients achieved remission, the shapes of the event-free survival curves were very similar for all three risk groups," Dr. Powell noted.

"Arsenic trioxide should be incorporated into therapy for patients with untreated acute promyelocytic leukemia," Dr. Powell concluded. "High-risk patients with white counts > 10,000 need better intial treatments to further reduce induction mortality. Arsenic trioxide does substantially reduce the relapse rate for this high-risk group."

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