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Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic
leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed
patients
ZX Shen, GQ Chen, JH Ni, XS Li, SM Xiong, QY Qiu, J Zhu, W Tang, GL Sun, KQ Yang, Y Chen, L Zhou, ZW Fang, YT Wang, J Ma, P Zhang, TD Zhang, SJ Chen, Z Chen and ZY Wang
Shanghai Institute of Hematology, Department of Hematology, Rui-Jin
Hospital, P.R. China.
The therapeutic effect of arsenic trioxide (As2O3) in the treatment of
acute promyelocytic leukemia (APL) was evaluated among 15 APL patients at
relapse after all-trans retinoic acid (ATRA) induced and chemotherapy
maintained complete remission (CR). As2O3 was administered intravenously at
the dose of 10 mg/d. Clinical CR was achieved in nine of 10 (90%) patients
treated with As2O3 alone and in the remaining five patients treated by the
combination of As2O3 and low-dose chemotherapeutic drugs or ATRA. During
the treatment with As2O3, there was no bone marrow depression and only
limited side effects were encountered. Pharmacokinetic studies, which were
performed in eight patients, showed that after a peak level of 5.54
micromol/L to 7.30 micromol/L, plasma arsenic was rapidly eliminated, and
the continuous administration of As2O3 did not alter its pharmacokinetic
behaviors. In addition, increased amounts of arsenic appeared in the urine,
with a daily excretion accounting for approximately 1% to 8% of the total
daily dose administered. Arsenic contents in hair and nail were increased,
and the peak content of arsenic could reach 2.5 to 2.7 microg/g tissue at
CR. On the other hand, a decline of the arsenic content in hair and nail
was observed after withdrawal of the drug. We conclude that As2O3 treatment
is an effective and relatively safe drug in APL patients refractory to ATRA
and conventional chemotherapy.
Volume 89,
Issue 9,
pp. 3354-3360,
05/01/1997
Copyright © 1997 by The American Society of Hematology

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|
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|
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|
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|
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[Full Text]
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|
 |
|

|
 |

|
 |
 
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109(2):
740 - 746.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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January 3, 2007;
99(1):
41 - 52.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Wetzler, M. T. Brady, E. Tracy, Z.-R. Li, K. A. Donohue, K. L. O'Loughlin, Y. Cheng, A. Mortazavi, A. A. McDonald, P. Kunapuli, et al.
Arsenic Trioxide Affects Signal Transducer and Activator of Transcription Proteins through Alteration of Protein Tyrosine Kinase Phosphorylation.
Clin. Cancer Res.,
November 15, 2006;
12(22):
6817 - 6825.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Dang, N. Kedersha, W.-K. Low, D. Romo, M. Gorospe, R. Kaufman, P. Anderson, and J. O. Liu
Eukaryotic Initiation Factor 2{alpha}-independent Pathway of Stress Granule Induction by the Natural Product Pateamine A
J. Biol. Chem.,
October 27, 2006;
281(43):
32870 - 32878.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Kimura, Y. Ishida, T. Hayashi, T. Wada, H. Yokoyama, T. Sugaya, N. Mukaida, and T. Kondo
Interferon-{gamma} Plays Protective Roles in Sodium Arsenite-Induced Renal Injury by Up-Regulating Intrarenal Multidrug Resistance-Associated Protein 1 Expression
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October 1, 2006;
169(4):
1118 - 1128.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Real-time PCR analysis of PML-RAR{alpha} in newly diagnosed acute promyelocytic leukaemia patients treated with arsenic trioxide as a front-line therapy
Ann. Onc.,
October 1, 2006;
17(10):
1553 - 1559.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Lemarie, C. Morzadec, E. Bourdonnay, O. Fardel, and L. Vernhet
Human macrophages constitute targets for immunotoxic inorganic arsenic.
J. Immunol.,
September 1, 2006;
177(5):
3019 - 3027.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Kannan-Thulasiraman, E. Katsoulidis, M. S. Tallman, J. S. C. Arthur, and L. C. Platanias
Activation of the Mitogen- and Stress-activated Kinase 1 by Arsenic Trioxide
J. Biol. Chem.,
August 11, 2006;
281(32):
22446 - 22452.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C.-W. Siu, W.-Y. Au, C. Yung, C. R. Kumana, C.-P. Lau, Y.-L. Kwong, and H.-F. Tse
Effects of oral arsenic trioxide therapy on QT intervals in patients with acute promyelocytic leukemia: implications for long-term cardiac safety
Blood,
July 1, 2006;
108(1):
103 - 106.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X.-F. Che, C.-L. Zheng, S. Owatari, M. Mutoh, T. Gotanda, H.-C. Jeung, T. Furukawa, R. Ikeda, M. Yamamoto, M. Haraguchi, et al.
Overexpression of survivin in primary ATL cells and sodium arsenite induces apoptosis by down-regulating survivin expression in ATL cell lines
Blood,
June 15, 2006;
107(12):
4880 - 4887.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Kojima, W. Qu, M. P. Waalkes, S. Himeno, and T. Sakurai
Chronic Exposure to Methylated Arsenicals Stimulates Arsenic Excretion Pathways and Induces Arsenic Tolerance in Rat Liver Cells
Toxicol. Sci.,
May 1, 2006;
91(1):
70 - 81.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. A. Kuryshev, L. Wang, B. A. Wible, X. Wan, and E. Ficker
Antimony-Based Antileishmanial Compounds Prolong the Cardiac Action Potential by an Increase in Cardiac Calcium Currents
Mol. Pharmacol.,
April 1, 2006;
69(4):
1216 - 1225.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
V. Mathews, B. George, K. M. Lakshmi, A. Viswabandya, A. Bajel, P. Balasubramanian, R. V. Shaji, V. M. Srivastava, A. Srivastava, and M. Chandy
Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity
Blood,
April 1, 2006;
107(7):
2627 - 2632.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J.-I Chao, S.-H. Hsu, and T.-C. Tsou
Depletion of Securin Increases Arsenite-Induced Chromosome Instability and Apoptosis via a p53-Independent Pathway
Toxicol. Sci.,
March 1, 2006;
90(1):
73 - 86.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L.-H. Yih, Y.-Y. Tseng, Y.-C. Wu, and T.-C. Lee
Induction of Centrosome Amplification during Arsenite-Induced Mitotic Arrest in CGL-2 Cells
Cancer Res.,
February 15, 2006;
66(4):
2098 - 2106.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Lemarie, C. Morzadec, D. Merino, O. Micheau, O. Fardel, and L. Vernhet
Arsenic Trioxide Induces Apoptosis of Human Monocytes during Macrophagic Differentiation through Nuclear Factor-{kappa}B-Related Survival Pathway Down-Regulation
J. Pharmacol. Exp. Ther.,
January 1, 2006;
316(1):
304 - 314.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Ghavamzadeh, K. Alimoghaddam, S. H. Ghaffari, S. Rostami, M. Jahani, R. Hosseini, A. Mossavi, E. Baybordi, A. Khodabadeh, M. Iravani, et al.
Treatment of acute promyelocytic leukemia with arsenic trioxide without ATRA and/or chemotherapy
Ann. Onc.,
January 1, 2006;
17(1):
131 - 134.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Kann, C. Estes, J. F. Reichard, M.-y. Huang, M. A. Sartor, S. Schwemberger, Y. Chen, T. P. Dalton, H. G. Shertzer, Y. Xia, et al.
Butylhydroquinone Protects Cells Genetically Deficient in Glutathione Biosynthesis from Arsenite-Induced Apoptosis Without Significantly Changing Their Prooxidant Status
Toxicol. Sci.,
October 1, 2005;
87(2):
365 - 384.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|