ASCO: Arsenic Trioxide Advances Survival for Acute Promyelocytic Leukemia

CHICAGO, June 4 -- Arsenic trioxide (Trisenox) improves survival for acute promyelocytic leukemia when added to first-line treatment, researchers said here.

Arsenic trioxide during consolidation treatment significantly lengthened overall survival (P=0.0346) and event-free survival (P=0.0011) over standard consolidation therapy alone, found Bayard L. Powell, M.D., of Wake Forest University Baptist Medical Center in Winston-Salem, N.C., and colleagues.

Although arsenic trioxide is approved for second-line remission and consolidation phase treatment among these patients, the study results suggest shifting to earlier use for high-risk patients, Dr. Powell said.

In a multicenter trial that included 480 adults with untreated APL, the patients received an induction regimen of oral tretinoin (Vesanoid, 45 mg/m²/d), daunorubicin (50 mg/m² IV for four days), and cytarabine (200 mg/m² for seven days), the investigators reported at the American Society of Clinical Oncology meeting here.

Patients were randomized to then act as controls or to receive two five-week cycles of arsenic trioxide given five days a week with a two week rest period between.

Both groups subsequently received two cycles of tretinoin and daunorubicin as further consolidation therapy.

Ninety percent of patients in both groups achieved complete or partial remission during induction treatment, which was required to go on to consolidation treatment.

At three years, overall survival was significantly better in the arsenic trioxide group than the control group (P=0.0346).

Event free survival was likewise significantly improved with arsenic trioxide compared with standard consolidation therapy alone (P=0.0011).

The best prognostic factor was an elevated white blood cell count of 10,000 or more, which defined a high-risk group, Dr. Powell said.

However, when these high-risk patients received arsenic trioxide their outcomes were similar to the lower-risk group, he added.

Only 2% of those who received at least one arsenic trioxide cycle had a leukemic relapse.

"This benefit occurs in all risk groups," he said, with "very little additional toxicity."

The findings reflect expanding treatment options that have come about with advances in knowledge of the underpinnings of cancer, commented Dean F. Bajorin, M.D., of Memorial Sloan-Kettering Cancer Center in New York.

"Our understanding of the molecular basis for cancer continues to expand," he said, "and with that knowledge comes a growing number of promising targeted therapies that attack cancer cells while leaving healthy cells intact."

While the mechanism of arsenic trioxide is not well understood, the drug appears to affect the promyelocytic leukemia gene on chromosome 15, Dr. Powell said.

Whatever the specific mechanism, he concluded, "arsenic trioxide should be incorporated into therapy for patients with untreated acute promyelocytic leukemia."

This recommendation may be particularly imperative for high-risk patients, he added.

"One thing that still needs to be improved is to change the initial treatment of patients with high white cell counts above 10,000, that high-risk group, so that more of those people can get to the arsenic trioxide and benefit from this consolidation treatment," he said.