september 2002: Bron: Journal of Clinical Oncology

Er is afgelopen tijd veel te doen geweest over het toepassen van een bepaalde vorm van arsenicum. Nu blijkt dat al eerder verschillende studies succes gaven te zien bij een bepaalde vorm van leukemie. 

1: J Clin Oncol 2001 Sep 15;19(18):3852-60
United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. College of Cornell University, New York, NY 10021, USA. soignets@mskcc.org

PATIENTS AND METHODS:
Forty patients experiencing first (n = 21) or > or = second (n = 19) relapse
were treated with daily infusions of ATO (arsenic trioxide) to a maximum of 60 doses 
or until all leukemic cells in bone marrow were eliminated. Patients who achieved a 
complete remission (CR) were offered one consolidation course of ATO that began 3 to 
4 weeks later. Patients who remained in CR were eligible to receive further cycles
of ATO therapy on a maintenance study. RESULTS: Thirty-four patients (85%)
achieved a CR. The 18-month overall and relapse-free survival (RFS)
estimates were 66% and 56%, respectively. Twenty patients (50%) had leukocytosis
(> 10,000 WBC/microL) during induction therapy. CONCLUSION: This study establishes 
ATO as a highly effective therapy for patients with relapsed APL.

PMID: 11559723 [PubMed - indexed for MEDLINE]
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1: Oncogene 2001 Oct 29;20(49):7146-53
Arsenic trioxide, a therapeutic agent for APL.

Over the past 5 years, it has been well demonstrated that Arsenic trioxide - As(2)O(3) induces a high complete remission (CR) rate in both primary and relapsed Acute promyelocytic leukemia (APL) patients (around 85 to 90%). The side effects are mild to moderate in relapsed patients, while severe hepatic lesions have been found in some primary 
cases. After CR obtained in relapsed patients, chemotherapy in combination with 
As(2)O(3) as post-remission therapy has given better survival than those treated 
with As(2)O(3) alone.
Cell biology studies have revealed that As(2)O(3) exerts dose-dependent dual effects 
on APL cells. Apoptosis is evident when cells are treated with 0.5 approximately 2.0 
microM of As(2)O(3) while partial differentiation is observed using low 
concentrations (0.1 approximately 0.5 microM) of the drug. The apoptosis-inducing 
effect is associated with the collapse of mitochondrial transmembrane potentials in 
a thiol-dependent manner, whereas the mechanisms underlying APL cell
differentiation induced by low dose arsenic remain to be explored.
Interestingly, As(2)O(3) over a wide range of concentration (0.1 approximately
2.0 microM) induces degradation of a key leukemogenic protein, PML-RARalpha, as
well as the wild-type PML, thus setting up a good example of targeting therapy
for human cancers.

PMID: 11704843 [PubMed - in process]




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