AUTHOR=Kumana Cyrus R. , Mak Raymond , Kwong Yok-Lam , Gill Harinder 

TITLE=Resurrection of Oral Arsenic Trioxide for Treating Acute Promyelocytic Leukaemia: A Historical Account From Bedside to Bench to Bedside

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.01294

DOI=10.3389/fonc.2020.01294

ISSN=2234-943X

ABSTRACT=<p>Various forms of arsenic were used in China and elsewhere for over 5,000 years. Following the initial success of intravenous arsenic trioxide (i.v. As<sub>2</sub>O<sub>3</sub>), we revived an oral formulation of pure As<sub>2</sub>O<sub>3</sub> in 1998 for the treatment of acute promyelocytic leukemia (APL). We were the first to produce a 1 mg/ml oral-As<sub>2</sub>O<sub>3</sub> solution and showed that it had comparable bioavailability to i.v. As<sub>2</sub>O<sub>3</sub>. Moreover, we also reported that intracellular arsenic concentrations were considerably higher than the corresponding plasma values. Our oral-As<sub>2</sub>O<sub>3</sub> was patented internationally and registered in Hong Kong for the treatment of APL. Safety, tolerability and clinical efficacy was confirmed in long-term follow-up studies. We have extended the use of oral-As<sub>2</sub>O<sub>3</sub> to frontline induction of newly diagnosed APL. With these findings, we are moving toward an era of completely oral and chemotherapy-free management of APL.</p>