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Arsenic trioxide

Approved for the treatment of M3 subtype of AML, acute promyelocytic leukemia that has relapsed or refractory to treatment.

More effective than all-trans retinoic acid (ATRA) in reducing the degree of minimal residual acute promyelocytic leukemic cells.

Most potent agent against promyelocytic leukemia with most patients achieving remission as assessed by PCR.

Side effects include gastrointestinal distress, elevation of liver enzymes, reversible neuropathy, hypokalemia, hyperglycemia and cardiac arrhythmias, hyperleukocytosis, and renal impairment.

Adverse effects of ATO include the following:

Prolongation of the QTc interval

Hepatotoxicity

Nausea and vomiting

Fluid retention

Itching and rash

APL differentiation syndrome

Liver dysfunction in 36% of treated patients.

Administered IV over 2 hours, but can be extended up to 4 hours if acute vasomotor reactions are present.

Administration via central venous catheter is not required.

QT prolongation in as many as 38% of treated patients.

Causes morphologic changes and DNA fragmentation in promyelocytic cells.

High complete remission rates in relapsed acute promyelocytic leukemia.

Introduction of this drug is most effective early in the course of promyelocytic leukemia

As a single agent induces molecular remission in almost all patients treated at relapse with APL (acute promyelocytic leukemia).

May be associated with the acute promyelocytic leukemia differentiation syndrome characterized by fever, dyspnea, weight gain, pulmonary infiltrates pleural and pericardial effusions with or without leukocytosis.

In newly diagnosed patients using PCR testing the number of PML/RARĪ± transcript copies is significantly lower than with ATRA.

In a study of 73 patients with untreated acute promyelocytic leukemia treatment resulted in a complete remission of 90%.

Use of this agent in APL associated with a relatively high incidence of leukocyte activation syndrome.

Paresthesias occur in 33% of individuals treated with this agent, but is rarely severe.

Recommended that potassium and magnesium levels be maintained at normal levels when using this agent.

Can cause QT interval prolongation, and can lead to torsades de pointes arrhythmia.

Prior to use electrolytes, creatinine and electrocardiogram should be performed.

QT values of greater than 500 msec required intervention to prevent arrhythmias.

Arsenic trioxide is an intravenous drug given daily for a prolonged period.

Arsenic trioxide is administered 5 days a week one month on and one month off, for a total of 8 months for APL.

Associated with a prolongation of the QT interval and risk for arrhythmias.

To prevent cardiac toxicity avoiding other QT-prolonging drugs, keeping magnesium, potassium within normal levels and providing magnesium and potassium foods or supplements are helpful.

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