Arsenic Improves Survival in Acute Promyelocytic Leukemia

Allison Gandey

June 15, 2007

June 15, 2007 (Chicago) — A randomized phase 3 trial has shown that adding arsenic trioxide to standard therapy significantly increases survival in newly diagnosed acute promyelocytic leukemia (APL). The findings were presented here at the American Society of Clinical Oncology 43rd Annual Meeting. "The differences in survival and relapse rates are great enough to justify including arsenic trioxide in standard first-line treatment," lead investigator Bayard Powell, MD, from Wake Forest University Baptist Medical Center, in Winston-Salem, North Carolina, told reporters. "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."

The researchers are part of the North American Intergroup Protocol known as C9710. They report that event-free survival at 3 years was 81% in the arsenic trioxide group and just 66% in those receiving standard therapy ( P = .0007). "This is very substantial," Dean Bajorin, MD, from Memorial Sloan-Kettering Cancer Center, in New York, and moderator of a news conference outlining the findings, told Medscape. "This is a manageable drug that can now be moved up front." During an interview, Dr. Bajorin said that he is not surprised by the findings given the efficacy arsenic trioxide has shown as a second-line therapy.

During the discussion period following the presentation, Bob Lowenberg, MD, from Erasmus University, in Rotterdam, the Netherlands, said the study investigators deserve credit for a significant effort. "They have written an important new page in the APL chapter," he said at the meeting. As a result of the work, Dr. Lowenberg noted, arsenic trioxide has been definitively established in the front-line therapy of APL. "The large, multicenter study shows significantly less relapse at the expense of limited extra toxicity." He added that studies like this are of "paramount clinical importance" for advancing therapy in rare forms of cancer like APL.

A subtype of acute myeloid leukemia, APL accounts for about 10% of cases. It is most often diagnosed in young and middle-aged adults. The researchers randomized roughly 500 patients. All participants received standard consolidation therapy, and about half of these received 2 courses of arsenic trioxide added to their treatment.

Response Observed in the North American Intergroup Protocol
Outcome
Arsenic Trioxide (n=243), n (%)
No Arsenic (n=237), n (%)
Complete remission
210 (86)
211 (89)
Partial remission
8 (3)
2 (1)
Total remission
218 (90)
213 (90)
Death during induction
16 (7)
16 (7)
No response
2 (1)
1 (0)
Insufficient data
7 (3)
7 (3)

Toxicity During Induction
Adverse Events
Grade 3 (%)
Grade 4 (%)
Hematologic
7
79
Nonhematologic
65
22

Toxicity During Consolidation
Adverse Events
Grade 3 (%)
Grade 4 (%)
Hematologic


  • Arsenic trioxide

20
55
  • No arsenic

16
67
Nonhematologic


  • Arsenic trioxide

42
5
  • No arsenic

30
5

During his presentation, Dr. Powell told attendees that the benefit observed with arsenic trioxide was observed in low-, intermediate-, and high-risk groups and was associated with acceptable toxicity.

Dr. Lowenberg said the next steps should be to identify better ways to exploit the therapeutic potential of arsenic trioxide and establish when and how to apply therapy. Many questions remain, he noted, such as whether the drug should be integrated as induction, consolidation, or maintenance therapy. He also wondered about optimal dose and how arsenic trioxide may better serve patients who are unable to take complete doses of chemotherapy.

ASCO 43rd Annual Meeting: Abstract 2. Presented June 4, 2007.

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