Treatment Protocol With Arsenic and Retinoic Acid Highly Effective for APL
Charlene Laino
Dec. 15, 2003 (San Diego) — A combination of all-trans retinoic acid (ATRA) and arsenic trioxide is more effective than either alone for treating patients with acute promyelocytic leukemia (APL), results of a new study suggest. The findings were presented here at the American Society of Hematology 45th Annual Meeting.
"While both agents have previously been shown to be effective in inducing clinical remissions in APL patients, our study shows the combination works even better," said Sai-Juan Chen, MD, an oncologist at the Shanghai Institute of Hematology in China.
Dr. Chen and a multicenter team randomized 61 newly diagnosed APL patients to remission induction and maintenance therapy with ATRA, arsenic, or a combination of the two. All three groups also received doxorubicin, cytarabine, and homoharrington, administered sequentially followed by ATRA maintenance. Chemotherapy was initiated if the peripheral white blood count was over 30 to 40 109 cells/L.
At a median follow-up of 15 months, all 20 patients in the combination therapy group remained in complete remission compared with only 30 of 37 patients treated with monotherapy (P < .05), Dr. Chen reported. Relapses occurred in 20% of patients in the ATRA arm and in 10% of those in the arsenic trioxide group, Dr. Chen said.
Also, the time to achieve a complete response was significantly lower in the combination treatment arm compared with either of the monotherapy arms (P < .001 and .01 for the ATRA and arsenic group, respectively).
One patient in the ATRA group died of treatment-related complications; otherwise adverse effects were about the same in all three groups.
Ronald Hoffman, MD, president of the American Society of Hematology and the Eileen Hiedrick Professor of Oncology and director of the Cancer Center at the University of Illinois College of Medicine in Chicago, told Medscape that the combination protocol could become the standard of care for patients with APL.
"Until now, we could expect over 90% of patients with APL to achieve a complete response, with 75% still disease-free at 2 years," he said. "With combination chemotherapy with all trans-retinoic acid and arsenic, we are able to improve on these rates."
According to Dr. Chen, the synergistic effect of ATRA and arsenic on apoptosis and degradation of PML-RAR alpha oncoprotein might explain why the combination therapy is better than treatment with either agent alone.
ASH 45th Annual Meeting: Abstract 486. Presented Dec. 8, 2003
Reviewed by Gary D. Vogin, MD
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