Sudden death among patients with acute promyelocytic leukemia treated with arsenic trioxide.
Arsenic trioxide has been shown to be effective in treating acute promyelocytic leukemia (APL), with minimal overall toxicity reported to date. A phase I/II study was initiated in June 1998 using arsenic trioxide for relapsed APL to determine the maximum tolerated or minimal effective dose and to determine the efficacy of treatment at that dose. Ten patients received 1 to 4 monthly cycles of treatment with 0.1 mg/kg per day intravenous arsenic trioxide. Six of 7 patients evaluable for response achieved cytogenetic or molecular complete remission. However, 3 patients died suddenly during the first cycle of treatment. Autopsies obtained on 2 of these failed to identify a cause of sudden death, despite evidence of pulmonary hemorrhage in one. A third patient, for whom an autopsy was not performed, became asystolic and died while on continuous cardiac telemetry. These observations suggest that arsenic trioxide may be significantly or even fatally toxic at doses currently used and that caution is warranted in its use.
Westervelt
P
P
Division of Bone Marrow Transplantation and Stem Cell Biology, and the Division of Molecular Oncology, Washington University School of Medicine, St Louis, MO 63110, USA. pwesterv@im.wustl.edu
Brown
R A
RA
Adkins
D R
DR
Khoury
H
H
Curtin
P
P
Hurd
D
D
Luger
S M
SM
Ma
M K
MK
Ley
T J
TJ
DiPersio
J F
JF
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D002648:Child; D003645:Death, Sudden; D005260:Female; D006801:Humans; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D012008:Recurrence
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide