NEW YORKLow doses of arsenic trioxide (ATO) given by
intravenous injection are highly effective at inducing remission in patients
with relapsed acute promyelocytic leukemia (APL) and should be tested in
patients with newly diagnosed disease. These results and recommendation were
based on research conducted at Memorial Sloan-Kettering Cancer Center (MSKCC)
in New York.
Steven L. Soignet, MD, lead investigator for the study and
director for Chemotherapy Practice at MSKCC, presented the combined results of
the US pilot and the multicenter trial of ATO in patients with relapsed APL.
Patients were treated with daily infusion of ATO until the time of bone marrow
complete remission. Patients who met all criteria for complete response (CR)
were then eligible to receive an additional 25 doses of ATO as consolidation.
"The addition of ATRA [all-trans-retinoic acid] to
chemotherapy for the treatment of APL has significantly improved the remission
rate and has more than doubled the overall survival compared to patients
treated with chemotherapy alone. Despite this advancement, 20%-30% of these
patients relapse," Dr. Soignet said. This study examined the efficacy of
ATO as an agent for inducing remissions in relapsed patients.
The study included 52 patients with a median age of 39 (range,
5-75) in either first (22), second (20), or third (10) relapse. Seven of
these patients were postallogeneic bone marrow transplant.
Overall Response of 87%
Dr. Soignet reported that 45 patients achieved a CR for an
overall response rate of 87%. In an interview with ONI, coinvestigator David
Scheinberg, MD, PhD, said previous studies by Chinese researchers and a US
pilot study "suggested that we would have a high response rate in
a larger study, and we did." Dr. Scheinberg is chief of the Leukemia
Service at MSKCC.
"ATO appears to down-regulate the actions of some of the
abnormal proteins found in APL that prevent normal maturation of the myeloid
cell. Once unblocked, the cells mature and die," Dr. Scheinberg said.
The median number of doses required for induction was 31
(range, 14-60). Of the 45 patients achieving a CR, 31 patients (69%) remain
alive at a median follow-up of 18 months. Of these survivors, 16 patients
received ATO as maintenance therapy only, and 15 patients underwent transplant.
Dr. Soignet said that toxicities were manageable and consisted
of mild hyperglycemia, QTc prolongation on electrocardiogram, peripheral
neuropathy, skin rash, leukocytosis, and APL syndrome. There were no
"We are now combining retinoic acid, monoclonal antibody
HuM195, and ATO before chemotherapy in an attempt to reduce and ultimately
eliminate the use of chemotherapy in this disease," Dr. Scheinberg said.