TRISENOX: Standard of care in relapsed or
refractory APL1
TRISENOX
® (arsenic trioxide) injection may give new hope to your relapsed or refractory
acute promyelocytic leukemia (APL) patients.
- TRISENOX delivers high rates of complete remission in relapsed or refractory APL2-4
- TRISENOX induces molecular remission in the majority of patients in relapse so chemotherapy is not required4
- TRISENOX is generally well tolerated, with manageable and reversible toxities4,5
- Low rate of grade 3 and 4 myelosuppression2,5
- No alopecia4
- Most common adverse events usually did not require interruption of TRISENOX5
- TRISENOX has multiple proposed mechanisms of action4, 6-10
- In APL, TRISENOX targets PML/RAR-alpha translocation
- TRISENOX may target other leukemic pathways to induce apoptosis
- TRISENOX offers a manageable dosing schedule that does not require premedication5
TRISENOX is indicated 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.
WARNING
Experienced Physician and Institution:
TRISENOX® (arsenic trioxide) injection should be administered under the supervision
of a physician who is experienced in the management of patients with acute leukemia.
APL Differentiation Syndrome:
Some patients with APL treated with TRISENOX have experienced symptoms similar to a
syndrome called the retinoic-acid-acute promyelocytic leukemia (RA-APL) or APL
differentiation syndrome, characterized by fever, dyspnea, weight gain, pulmonary
infiltrates and pleural or pericardial effusions, with or without leukocytosis. This
syndrome can be fatal. The management of the syndrome has not been fully studied, but
high-dose steroids have been used at the first suspicion of the APL differentiation
syndrome and appear to mitigate signs and symptoms. At the first signs that could suggest
the syndrome (unexplained fever, dyspnea and/or weight gain, abnormal chest auscultatory
findings or radiographic abnormalities), high-dose steroids (dexamethasone 10 mg
intravenously BID) should be immediately initiated, irrespective of the leukocyte count,
and continued for at least 3 days or longer until signs and symptoms have abated. The
majority of patients do not require termination of TRISENOX therapy during treatment of
the APL differentiation syndrome.
ECG Abnormalities:
Arsenic trioxide can cause QT interval prolongation and complete atrioventricular
block. QT prolongation can lead to a torsade de pointes-type ventricular arrhythmia,
which can be fatal. The risk of torsade de pointes is related to the extent of QT
prolongation, concomitant administration of QT prolonging drugs, a history of torsade
de pointes, pre-existing QT interval prolongation, congestive heart failure,
administration of potassium-wasting diuretics, or other conditions that result in
hypokalemia or hypomagnesemia. One patient (also receiving amphotericin B) had
torsade de pointes during induction therapy for relapsed APL with arsenic trioxide.
ECG and Electrolyte Monitoring Recommendations:
Prior to initiating therapy with TRISENOX, a 12-lead ECG should be performed and
serum electrolytes (potassium, calcium, and magnesium) and creatinine should be
assessed; pre-existing electrolyte abnormalities should be corrected and, if
possible, drugs that are known to prolong the QT interval should be discontinued.
For QTc greater than 500 msec, corrective measures should be completed and the
QTc reassessed with serial ECGs prior to considering using TRISENOX. During
therapy with TRISENOX, potassium concentrations should be kept above 4 mEq/L and
magnesium concentrations should be kept above 1.8 mg/dL. Patients who reach an
absolute QT interval value > 500 msec should be reassessed and immediate action
should be taken to correct concomitant risk factors, if any, while the risk/benefit
of continuing versus suspending TRISENOX therapy should be considered. If syncope,
rapid or irregular heartbeat develops, the patient should be hospitalized for
monitoring, serum electrolytes should be assessed, TRISENOX therapy should be
temporarily discontinued until the QTc interval regresses to below 460 msec,
electrolyte abnormalities are corrected, and the syncope and irregular heartbeat
cease. There are no data on the effect of TRISENOX on the QTc interval during the
infusion.
1. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Acute Myeloid Leukemia — v.2.2007.
2. Soignet SL, Frankel SR, Douer D, et al. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol. 2001;19:3852-3860.
3. Soignet SL, Maslak P, Wang Z-G, et al. Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. N Engl J Med. 1998;339:1341-1348.
4. Douer D, Tallman MS. Arsenic trioxide: new clinical experience with an old medication in hematologic malignancies. J Clin Oncol. 2005;23:2396-2410.
5. TRISENOX Prescribing Information. Frazer, Pa: Cephalon, Inc.;2005.
6. 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.
7. Hayakawa F, Privalsky M. Phosphorlyation of PML by mitogen-activated protein kinases plays a key role in arsenic trioxide-mediated apoptosis. Cancer Cell. 2004;5:389-401.
8. Mann K, Miller W. Death by arsenic: implications of PML sumoylation. Cancer Cell. 2004;5:307-309.
9. Davison K, Mann KK, Miller WH Jr. Arsenic trioxide: mechanisms of action. Semin Hematol. 2002;39(2 Suppl 1):3-7.
10. Miller WH Jr. Molecular targets of arsenic trioxide in malignant cells. Oncologist. 2002;7 Suppl 1:14-19.