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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
Abstract
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 μmol/L to 7.30 μmol/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 μg/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.
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Cited by
Retinoic Acid and Arsenic Trioxide for Acute Promyelocytic Leukemia
Lo-Coco, F., Avvisati, G., Vignetti, M., Thiede, C., Orlando, S. M., Iacobelli, S., Ferrara, F., Fazi, P., Cicconi, L., Di Bona, E., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1300874 · Cited by 1,611
Functional genomic landscape of acute myeloid leukaemia
Tyner, J. W., Tognon, C. E., Bottomly, D., Wilmot, B., Kurtz, S. E., Savage, S. L., Long, N., Schultz, A. R., Traer, E., Abel, M., et al. (2018) · Nature · doi:10.1038/s41586-018-0623-z · Cited by 1,303
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Ratnaike, R. N. (2003) · Postgraduate Medical Journal · doi:10.1136/pmj.79.933.391 · Cited by 1,175
PML targeting eradicates quiescent leukaemia-initiating cells
Ito, K., Bernardi, R., Morotti, A., Matsuoka, S., Saglio, G., Ikeda, Y., Rosenblatt, J., Avigan, D. E., Teruya-Feldstein, J., & Pandolfi, P. P. (2008) · Nature · doi:10.1038/nature07016 · Cited by 538
Inhibition of Mitochondrial Respiration
Pelicano, H., Feng, L., Zhou, Y., Carew, J. S., Hileman, E. O., Plunkett, W., Keating, M. J., & Huang, P. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301546200 · Cited by 495
Metadata
- Authors
- Shen, Z.-X., Chen, G.-Q., Ni, J.-H., Li, X.-S., Xiong, S.-M., Qiu, Q.-Y., Zhu, J., Tang, W., Sun, G.-L., Yang, K.-Q., Chen, Y., Zhou, L., Fang, Z.-W., Wang, Y.-T., Ma, J., Zhang, P., Zhang, T.-D., Chen, S.-J., Chen, Z., & Wang, Z.-Y.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 1997-05-01
- Volume
- 89
- Issue
- 9
- Pages
- 3354-3360
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2142423276
- Cited by
- 1,428
- References
- 0
- FWCI
- 11.70
- Type
- journal article
- Language
- en
- Open access
- closed
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- Shen, Z.-X., Chen, G.-Q., Ni, J.-H., Li, X.-S., Xiong, S.-M., Qiu, Q.-Y., Zhu, J., Tang, W., Sun, G.-L., Yang, K.-Q., Chen, Y., Zhou, L., Fang, Z.-W., Wang, Y.-T., Ma, J., Zhang, P., Zhang, T.-D., Chen, S.-J., Chen, Z., & Wang, Z.-Y. (1997). Use of Arsenic Trioxide (As2O3 ) in the Treatment of Acute Promyelocytic Leukemia (APL): II. Clinical Efficacy and Pharmacokinetics in Relapsed Patients. Blood. https://doi.org/10.1182/blood.v89.9.3354
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