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, preexisting 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; preexisting 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.
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TRISENOX SUMMARY
TRISENOX® is a sterile injectable solution of arsenic trioxide.
TRISENOX® is indicated for induction of remission and consolidation in patients with acute promyelocytic leukemia (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.
The response rate of other acute myelogenous leukemia subtypes to TRISENOX® has not been examined.
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NEWS HIGHLIGHTS
Published Studies Related to Trisenox (Arsenic Trioxide)
The efficacy of arsenic trioxide for the treatment of relapsed and refractory multiple myeloma: a systematic review. [2009.08]
Arsenic trioxide (ATO) has been proposed as an option for the treatment of relapsing or refractory multiple myeloma. In order to critically appraise the published clinical evidence, a systematic search of the databases PubMed, Embase, Web of Science and the Cochrane Library was performed.With respect to the higher evidence level of new substances such as bortezomib or lenalidomide, at present ATO has no role in routine management of relapsed or refractory myeloma.
A phase I/II study of arsenic trioxide/bortezomib/ascorbic acid combination therapy for the treatment of relapsed or refractory multiple myeloma. [2007.03.15]
CONCLUSIONS: The ABC regimen was well tolerated by most patients, and it produced preliminary signs of efficacy with an objective response rate of 27% in this heavily pretreated study population. These findings warrant further clinical evaluation of the ABC combination for treatment of relapsed/refractory multiple myeloma.
[Clinical observation and following up of two administration methods of arsenic trioxide in treatment of acute promyelocytic leukemia] [2004.03.02]
OBJECTIVE: To assess the effectiveness and security of two arsenic trioxide (As(2)O(3)) administration methods in treatment of acute promyelocytic leukemia (APL)... CONCLUSION: The 'multi-times and slowing intravenous infusion' method relieves the side effects of As(2)O(3) treatment, increases the CR rate in treatment of APL.
Combined treatment with arsenic trioxide and all-trans-retinoic acid in patients with relapsed acute promyelocytic leukemia. [2003.06.15]
PURPOSE: Arsenic trioxide (ATO) is capable of inducing a high hematologic response rate in patients with relapsed acute promyelocytic leukemia (APL). Preclinical observations have indicated that all-trans-retinoic acid (ATRA) may strongly enhance the response to ATO... CONCLUSION: ATRA did not seem to significantly improve the response to ATO in patients relapsing from APL. Other potential combinations, including ATO plus chemotherapy, have to be tested.
[An analysis of the therapeutic effects and reactions in treating acute promyelocytic leukemia with intravenous arsenic trioxide or all-trans retinoic acid] [1999.02]
OBJECTIVE: To compare the therapeutic effects and reactions of intra venous arsenic trioxide and all-trans retinoic acid in treating patients with acute promyelocytic leukemia (APL)... CONCLUSION: Arsenic trioxide can lead to apoptosis of leukemic cells and might be a new promising drug to induce differentiation.
Clinical Trials Related to Trisenox (Arsenic Trioxide)
Arsenic Trioxide With Ascorbic Acid and Melphalan for Myeloma Patients [Completed]
1. To evaluate the toxicity and safety of a combination of arsenic trioxide with ascorbic
acid and high-dose Melphalan in patients with multiple myeloma
2. To evaluate the efficacy of a combination of arsenic trioxide with ascorbic acid and
high-dose Melphalan in patients with multiple myeloma
3. To determine the effects of arsenic trioxide on melphalan pharmacokinetics
Velcade, Trisenox, Vitamin C and Melphalan for Myeloma Patients [Active, not recruiting]
Primary Objectives:
1. To evaluate the toxicity and safety of a combination of bortezomib with arsenic
trioxide, ascorbic acid and high-dose melphalan in patients with multiple myeloma
2. To evaluate the efficacy of a combination of bortezomib with arsenic trioxide, ascorbic
acid and high-dose melphalan in patients with multiple myeloma
3. To determine the effects of bortezomib on melphalan pharmacokinetics
Phase II Research Study of Arsenic Trioxide (Trisenox) in Patients With Myelodysplastic Syndrome (MDS) [Terminated]
In this phase II study besides evaluating for safety, the primary efficacy parameter is to
evaluate the incidence of patients who have had a response to Trisenox by evidence of
increased blood counts (red, white, or platelets) and/or by decrease or transfusion
dependency. The secondary efficacy parameter is the assessment of the tolerability of the
new dosing schedule.
Arsenic trioxide will be administered intravenously over 1 to 2 hours with a loading dose of
0. 30mg/kg for days 1-5 of the first week and then twice weekly for 27 weeks for a total of 28
weeks.
Liposomal Doxorubicin, Vincristine, & Dexamethasone Plus Arsenic Trioxide in Untreated Symptomatic Multiple Myeloma [Suspended]
This study will assess the ability of Doxorubicin, Vincristine and Dexamethasone plus
arsenic trioxide to achieve an overall response rate of greater than 60%.
A Phase II Protocol of Arsenic Trioxide (Trisenox) in Subjects With Advanced Primary Carcinoma of the Liver [Recruiting]
The purpose of this study is: evaluate the safety and activity of administering arsenic
trioxide (Trisenox) in the treatment of unresectable or metastatic primary liver cancer, to
evaluate the qualitative and quantitative toxicities of this treatment, and to measure the
response to treatment and the patterns of failure and survival. The primary response
measurements will be the achievement of an objective tumor response, response duration and
progression-free survival
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Page last updated: 2009-10-20
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