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 (As(2)O(3)) is effective in this setting. The authors report the experience of The M. D. Anderson Cancer Center with As(2)O(3) in the treatment of patients with recurrent APL.


METHODS
Twelve patients who developed recurrent APL after treatment with ATRA were included. Patients received intravenous As(2)O(3) 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 post-remission therapy. All patients received subsequent therapy: Four patients received As(2)O(3) alone, six patients received As(2)O(3) with other chemotherapeutic agents, and two patients received idarubicin plus ATRA without As(2)O(3). 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
As(2)O(3) 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.
Lazo
Guillermo
G
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Kantarjian
Hagop
H
Estey
Elihu
E
Thomas
Deborah
D
O'Brien
Susan
S
Cortes
Jorge
J
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005500:Follow-Up Studies; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D010087:Oxides / Q000009:adverse effects / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D012074:Remission Induction; D012449:Safety; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001152:Arsenicals; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D010087:Oxides; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D000077237:Arsenic Trioxide