Chinese Give Arsenic Plus Tretinoin Up Front for APL

• ORLANDO—Four years of follow-up have confirmed that the front-line combination of all-trans-retinoic acid, or ATRA (tretinoin, Vesanoid), and arsenic trioxide (Trisenox) is beneficial for the treatment of patients with newly diagnosed acute promyelocytic leukemia (APL), Zhu Chen, MD, of the Department of Hematology, Shanghai University, China, said at the American Society of Hematology 48th Annual Meeting (abstract 565). The researchers, led by Yuan-Fang Liu, MD, also of Shanghai University, compared 60 newly diagnosed APL patients, treated since April 2001 with the combination regimen, with a historical cohort of 56 patients treated from May 1998 to March 2001 with tretinoin alone.

The combination group received tretinoin 25 mg/m² orally and arsenic trioxide 0.16 mg/kg intravenously daily until a complete response was achieved. Then they received three courses of consolidation chemotherapy followed by five cycles of sequential treatment with tretinoin, arsenic trioxide, and 6-mercaptopurine/methotrexate. The historical group received tretinoin 25 mg/m² daily until a complete response was achieved. Chemotherapy was added in case of leukocytosis in this cohort. Postremission therapy consisted of chemotherapy with or without tretinoin.

Among the combination patients, 56 (93.3%) achieved a complete response in a median time of 27 days. Four-year overall and event-free survival rates for the combination group were 98.1% and 94.2%, respectively. For the historical group, with a median follow-up of 56 months, the rates were 83.4% and 45.6%, respectively (P < .00001).

Charles A. Linker, MD, clinical professor of medicine, University of California, San Francisco, commented: "The use of ATRA [tre-tinoin] combined with chemotherapy has been the standard of care in APL and this has been a tremendous advance. The Shanghai team has incorporated arsenic trioxide and given it with ATRA up front, and then followed it with traditional chemotherapy. They have shown remarkable success. With 53 of 56 patients remaining in remission with this therapy, the outlook for these patients is very promising."

Dr. Chen added: "The protocol is simple and convenient enough to be carried out, even in an outpatient department, and this significantly improves the quality of life. With prolonged follow-up, we hope that we can define a curative treatment for this disease."