Targeted mechanisms of action
"APL is uniquely sensitive to the apoptotic and differentiating effects of arsenic trioxide"1
- Douer D, Tallman MS. J Clin Oncol. 2005;23:2396-2410
TRISENOX
® (arsenic trioxide) injection has multiple proposed mechanisms of action:
- TRISENOX degrades the PML/RAR-alpha protein, releasing the maturation block to enable partial differentiation1,2
- Through its effect on the PML/RAR-alpha fusion protein and directly on PML, TRISENOX may reactivate the tumor-suppression and pro-apoptotic functions of the PML gene3,4
- TRISENOX may cause the accumulation of toxic free radicals inside the APL cell, which triggers apoptosis, or self-destruction5,6
The mechanisms of action of TRISENOX are not completely understood and are being actively studied.
7
>> Click here to view the efficacy data for TRISENOX.
In clinical trials, most patients taking TRISENOX experienced some drug-related toxicity,
most commonly leukocytosis, gastrointestinal (nausea, vomiting, diarrhea, and abdominal pain),
fatigue, edema, hyperglycemia, dyspnea, cough, rash or itching, headaches, and dizziness.
These adverse effects have not been observed to be permanent or irreversible, nor do they
usually require interruption of therapy.
1. Douer D, Tallman MS. Arsenic trioxide: new clinical experience with an old medication in hematologic malignancies. J Clin Oncol. 2005;23:2396-2410.
2. Chen G-Q, Shi X-G, Tang W, et al. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): I. As2O3 exerts dose-dependent dual effects on APL cells. Blood. 1997;89:3345-3353.
3. Hayakawa F, Privalsky ML. Phosphorlyation of PML by mitogen-activated protein kinases plays a key role in arsenic trioxide-mediated apoptosis. Cancer Cell. 2004;5:389-401.
4. Mann K, Miller W. Death by arsenic: implications of PML sumoylation. Cancer Cell. 2004;5:307-309.
5. Davison K, Mann KK, Miller WH Jr. Arsenic trioxide: mechanisms of action. Semin Hematol. 2002;39(2 Suppl 1):3-7.
6. Miller WH Jr. Molecular targets of arsenic trioxide in malignant cells. Oncologist. 2002;7 Suppl 1:14-19.
7. TRISENOX Prescribing Information. Frazer, Pa: Cephalon, Inc.;2005.