Single-Agent Arsenic Trioxide in the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia: Long-Term Follow-Up Data

Abstract

PURPOSE We previously reported our results with a single-agent arsenic trioxide (ATO) -based regimen in newly diagnosed cases of acute promyelocytic leukemia (APL). The concern remained about the long-term outcome of this well-tolerated regimen. We report our long-term follow-up data on the same cohort. PATIENTS AND METHODS From January 1998 to December 2004, 72 patients with PML/RARalpha+ APL were enrolled. All patients were treated with a single-agent ATO regimen. Results Overall 62 (86.1%) achieved a hematologic remission (complete remission). After the initial report, an additional seven patients have relapsed for a total of 13 relapses. There were no additional toxicities to report on follow-up. At a median follow-up 60 months, the 5-year Kaplan-Meier estimate (+/- SE) of event-free survival, disease-free survival, and overall survival (OS) was 69% +/- 5.5%, 80% +/- 5.2%, and 74.2% +/- 5.2%, respectively. The OS in the good risk group as defined by us remains 100% over this period. CONCLUSION Single-agent ATO as used in this study in the management of newly diagnosed cases of APL is safe and is associated with durable responses. Results in the low-risk group are comparable to that reported with conventional therapy while additional interventions would probably be required in high-risk cases.

PML nuclear bodies: Assembly and oxidative stress-sensitive sumoylation

“…47 Future studies should further delineate the arsenic/PML interactions, as they clearly underlie therapeutic response and cure of APL upon arsenic therapy (see below). 84 PML NBs were once envisioned as simple depots where cellular or viral proteins were sequestered or stored. 85,86 Yet, a more complex view has recently emerged wherein sumoylated partners may be modified by other NB-associated enzymes, particularly enzymes controlling various post-translational modifications.…”

The Drug-Induced Degradation of Oncoproteins: An Unexpected Achilles' Heel of Cancer Cells?

“…This model has been progressively questioned by several subsequent findings. In particular, arsenic treatment, which does not directly activate PML/RARA-dependent transcription and fails to induce significant ex vivo differentiation, can cure up to 70% of patients when used as single agent (51)(52)(53)(54). Similarly, although the RA-arsenic combination antagonizes differentiation ( 51 ), it is actually synergistic with regard to APL cell clearance, culminating in disease eradication in mice as well as in humans ( 21 , 55 ).…”

Radiosensitization of cervical cancer xenografts by arsenic trioxide and the role of VEGF and Ku70

“…Clearly, strategies for further improvement of therapeutic ratio in the management of cervical cancer with radiation-based treatment are needed. As 2 O 3 is an agent successfully employed in the treatment of APL with limited side effects [11][12][13]. It was found to induce growth inhibition and apoptosis in solid tumors [19,20].…”

“…It has been used to treat a variety of conditions including cancer [9,10]. As 2 O 3 has been proven efficacious in the treatment of acute promyelocytic leukemia (APL) with limited adverse effects [11][12][13]. It has been demonstrated that As 2 O 3 can affect cellular signal transduction pathways and cross-talks of signal molecules which include downregulation of Bcl-2 protein, activation of caspase, direct mitochondrial damage, promotion of tubulin polymerization [14], and some of the abovementioned mechanisms are involved in radiosensitization.…”