General Information

Trisenox (arsenic trioxide) is an arsenical.

Trisenox is indicated:

In combination with tretinoin for treatment of adults with newly-diagnosed low-risk acute promyelocytic leukemia (APL) whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.

For induction of remission and consolidation in patients with APL who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression

Trisenox is supplied as an intravenous injection. The recommended dosing is as follows:

Newly-diagnosed low-risk APL:

• Induction: Administer 0.15 mg/kg/day intravenously daily in combination with tretinoin until bone marrow remission. Do not exceed 60 days.
• Consolidation: Administer 0.15 mg/kg/day intravenously daily for 5 days per week during weeks 1-4 of each 8-week cycle for a total of 4 cycles in combination with tretinoin.

 Relapsed or refractory APL:

• Induction: Administer 0.15 mg/kg/day intravenously daily until bone marrow remission. Do not exceed 60 days.
• Consolidation: Administer 0.15 mg/kg/day intravenously daily for 25 doses over a period of up to 5 weeks.

Mechanism of Action

The mechanism of action of Trisenox is not completely understood. Arsenic trioxide causes morphological changes and DNA fragmentation characteristic of apoptosis in NB4 human promyelocytic leukemia cells in vitro. Arsenic trioxide also causes damage or degradation of the fusion protein PML-RAR alpha. 

Side Effects

Common side effects include, but are not limited to:

• leukocytosis
• nausea
• vomiting
• diarrhea
• abdominal pain
• fatigue
• edema
• hyperglycemia
• dyspnea
• cough
• rash or itching
• headaches
• dizziness

The Trisenox drug label comes with the following Black Box Warning: Patients with acute promyelocytic leukemia (APL) treated with Trisenox have experienced symptoms of differentiation syndrome, which may be life-threatening or fatal. If differentiation syndrome is suspected, immediately initiate high-dose corticosteroids and hemodynamic monitoring until resolution. Temporarily withhold Trisenox. Trisenox can cause QTc interval prolongation, complete atrioventricular block and torsade de pointes, which can be fatal. Before administering Trisenox, assess the QTc interval, correct electrolyte abnormalities, and consider discontinuing drugs known to prolong QTc interval. Do not administer Trisenox to patients with ventricular arrhythmia or prolonged QTc interval. Withhold Trisenox until resolution and resume at reduced dose for QTc prolongation. Serious encephalopathy, including Wernicke’s, has occurred with Trisenox. If Wernicke’s encephalopathy is suspected, immediately interrupt Trisenox and initiate parenteral thiamine. Monitor until symptoms resolve or improve and thiamine levels normalize.

Clinical Trial Results

A multi-center pivotal trial was held, led by Memorial Sloan-Kettering Cancer Center, consisting of 40 patients ranging in age from 5 to 72. The drug was shown to be effective with 70% of the patients achieving complete remission. 86% showed clearing of the chromosomal abnormality that causes APL. Total remission was reached, on average, within two months after treatment with Trisenox began. At a median follow-up time of 16 months, 68% of patients who had achieved complete remission were still alive and 58% were disease free.