Safety and efficacy of arsenic trioxide for patients with advanced metastatic melanoma

Tarhini, Ahmad A.; Kirkwood, John M.; Tawbi, Hussein A.; Gooding, William E.; Islam, Mohammed; Agarwala, Sanjiv S.

doi:10.1002/cncr.23284

Cited by 24 publications

(19 citation statements)

References 30 publications

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“…Therefore, a baseline 12‐lead ECG and electrolyte levels are recommended. Concomitant QT‐prolonging agents should be discontinued, and electrolytes should be normal before and during treatment 133. If QTc increases to >500 ms, continuation of arsenic trioxide should be carefully evaluated.…”

Section: Resultsmentioning

confidence: 99%

Incidence, Diagnosis, and Management of QT Prolongation Induced by Cancer Therapies: A Systematic Review

Porta‐Sánchez

Gilbert

Spears

et al. 2017

JAHA

154

142

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BackgroundThe cardiovascular complications of cancer therapeutics are the focus of the burgeoning field of cardio‐oncology. A common challenge in this field is the impact of cancer drugs on cardiac repolarization (ie, QT prolongation) and the potential risk for the life‐threatening arrhythmia torsades de pointes. Although QT prolongation is not a perfect marker of arrhythmia risk, this has become a primary safety metric among oncologists. Cardiologists caring for patients receiving cancer treatment should become familiar with the drugs associated with QT prolongation, its incidence, and appropriate management strategies to provide meaningful consultation in this complex clinical scenario.Methods and ResultsIn this article, we performed a systematic review (using Preferred Reporting Items of Systematic Reviews and Meta‐Analyses (PRISMA) guidelines) of commonly used cancer drugs to determine the incidence of QT prolongation and clinically relevant arrhythmias. We calculated summary estimates of the incidence of all and clinically relevant QT prolongation as well as arrhythmias and sudden cardiac death. We then describe strategies to prevent, identify, and manage QT prolongation in patients receiving cancer therapy. We identified a total of 173 relevant publications. The weighted incidence of any corrected QT (QTc) prolongation in our systematic review in patients treated with conventional therapies (eg, anthracyclines) ranged from 0% to 22%, although QTc >500 ms, arrhythmias, or sudden cardiac death was extremely rare. The risk of QTc prolongation with targeted therapies (eg, small molecular tyrosine kinase inhibitors) ranged between 0% and 22.7% with severe prolongation (QTc >500 ms) reported in 0% to 5.2% of the patients. Arrhythmias and sudden cardiac death were rare.ConclusionsOur systematic review demonstrates that there is variability in the incidence of QTc prolongation of various cancer drugs; however, the clinical consequence, as defined by arrhythmias or sudden cardiac death, remains rare.

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Section: Resultsmentioning

confidence: 99%

Incidence, Diagnosis, and Management of QT Prolongation Induced by Cancer Therapies: A Systematic Review

Porta‐Sánchez

Gilbert

Spears

et al. 2017

JAHA

154

142

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“…The usual dose used to treat APL is 0.15 mg/kg/d, and larger doses (up to 35 mg/kg/d) have been used in phase II clinical trials in patients with metastatic melanoma and renal cell carcinoma (38)(39)(40). In mice and rats, the usual doses ranged from 2 to 8 mg/kg (28,30) and generally exceed the doses used in humans.…”

Section: Discussionmentioning

confidence: 99%

Arsenic Trioxide Treatment Decreases the Oxygen Consumption Rate of Tumor Cells and Radiosensitizes Solid Tumors

et al. 2012

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Arsenic trioxide (As 2 O 3 ) is an effective therapeutic against acute promyelocytic leukemia and certain solid tumors. Because As 2 O 3 inhibits mitochondrial respiration in leukemia cells, we hypothesized that As 2 O 3 might enhance the radiosensitivity of solid tumors by increasing tumor oxygenation [partial pressure of oxygen (pO 2 )] via a decrease in oxygen consumption. Two murine models of radioresistant hypoxic cancer were used to study the effects of As 2 O 3 . We measured pO 2 and the oxygen consumption rate in vivo by electron paramagnetic resonance oximetry and 19 fluorine-MRI relaxometry. Tumor perfusion was assessed by Patent blue staining. In both models, As 2 O 3 inhibited mitochondrial respiration, leading to a rapid increase in pO 2 . The decrease in oxygen consumption could be explained by an observed decrease in glutathione in As 2 O 3 -treated cells, as this could increase intracellular reactive oxygen species that can disrupt mitochondrial membrane potential. When tumors were irradiated during periods of As 2 O 3 -induced augmented oxygenation, radiosensitivity increased by 2.2-fold compared with control mice. Notably, this effect was abolished when temporarily clamped tumors were irradiated. Together, our findings show that As 2 O 3 acutely increases oxygen consumption and radiosensitizes tumors, providing a new rationale for clinical investigations of As 2 O 3 in irradiation protocols to treat solid tumors. Cancer Res; 72(2); 482-90. Ó2011 AACR.

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“…Limited clinical activity as a single agent has been reported in a small number of patients with HCC,75 melanoma,76,77 and renal cell carcinoma78; As 2 O 3 in combination with chemotherapy has shown promising activity in osteosarcoma and Ewing sarcoma 79…”

Section: Efficacy Of As2o3 In Other Malignanciesmentioning

confidence: 99%

Arsenic trioxide — An old drug rediscovered

2010

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Over the last 17 years, clinical trials conducted worldwide have demonstrated the efficacy of arsenic trioxide (As 2 O 3 ) in the treatment of relapsed acute promyelocytic leukemia (APL). Currently, the role of As 2 O 3 in front-line therapy is under investigation. Recent trials in the US have demonstrated that the addition of As 2 O 3 to standard treatment regimens improves survival outcomes in patients with APL and may allow a reduction in cytotoxic chemotherapy exposure. As 2 O 3 has also shown efficacy in other malignancies, particularly multiple myeloma and myelodysplastic syndromes. Therapeutic doses of As 2 O 3 are well tolerated, with no evidence of long-term toxicity. Adverse events include APL differentiation syndrome, electrocardiographic abnormalities, and mild elevations in liver enzymes. This review highlights trials investigating the role of As 2 O 3 in induction and consolidation for newly diagnosed APL, as well as its role in other hematologic malignancies. The chemistry, mechanisms of action, and clinical side effects of As 2 O 3 are also discussed.

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Safety and efficacy of arsenic trioxide for patients with advanced metastatic melanoma

Cited by 24 publications

References 30 publications

Incidence, Diagnosis, and Management of QT Prolongation Induced by Cancer Therapies: A Systematic Review

Incidence, Diagnosis, and Management of QT Prolongation Induced by Cancer Therapies: A Systematic Review

Arsenic Trioxide Treatment Decreases the Oxygen Consumption Rate of Tumor Cells and Radiosensitizes Solid Tumors

Arsenic trioxide — An old drug rediscovered

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