Use of arsenic trioxide (As2O3) in the treatment of patients with acute promyelocytic leukemia: The M. D. Anderson experience

BACKGROUND Approximately 20–30% of patients with acute promyelocytic leukemia (APL) who are treated with all-trans retinoic acid (ATRA) and an anthracycline develop recurrent disease. It has been reported that arsenic trioxide (As2O3) is effective in this setting. The authors report the experience of The M. D. Anderson Cancer Center with As2O3 in the treatment of patients with recurrent APL. METHODS Twelve patients who developed recurrent APL after treatment with ATRA were included. Patients received intravenous As2O3 0.15 mg/kg per day until they achieved a complete remission (CR) or up to a maximum of 60 days. Their median age was 44 years (range, 26–72 years), and the median duration of first remission was 52 weeks (range, 23–292 weeks). RESULTS All 12 patients achieved a CR. The median time to achieve CR was 52 days (range, 27–75 days). Seven of 10 evaluable patients achieved a molecular remission (i.e., polymerase chain reaction [PCR] analysis was negative for the gene encoding fusion of the nuclear receptor for retinoic acid to the PML gene at the time of CR; 70% of patients; 95% confidence interval, 0.35–0.93), and all other patients had negative PCR results after they received postremission therapy. All patients received subsequent therapy: Four patients received As2O3 alone, six patients received As2O3 with other chemotherapeutic agents, and two patients received idarubicin plus ATRA without As2O3. Eight patients continued in CR after a median follow-up of 24 months (range, 9–45 months). Side effects were mild, except for two patients who developed Grade 2 and 3 peripheral neuropathy, respectively; one of those patients required discontinuation of therapy. CONCLUSIONS As2O3 is effective and well tolerated therapy for patients with recurrent APL. Molecular remission may be achieved at the time of CR in the majority of patients, and remissions are durable. Cancer 2003;97:2218–24. © 2003 American Cancer Society. DOI 10.1002/cncr.11314