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

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. AsO), we revived an oral formulation of pure AsO in 1998 for the treatment of acute promyelocytic leukemia (APL). We were the first to produce a 1 mg/ml oral-AsO solution and showed that it had comparable bioavailability to i.v. AsO. Moreover, we also reported that intracellular arsenic concentrations were considerably higher than the corresponding plasma values. Our oral-AsO 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-AsO 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.