Pi Shuang

Phase 3 randomised non-inferiority trial in 162 adults with newly diagnosed low-to-intermediate risk acute promyelocytic leukaemia comparing all-trans retinoic acid plus intravenous arsenic trioxide with ATRA plus idarubicin. Two-year event-free survival was 97 percent with ATRA-arsenic versus 86 percent with ATRA-chemotherapy, establishing the chemotherapy-free arsenic regimen as standard of care. This is the evidence base for pharmaceutical-grade arsenic trioxide given intravenously under haematology supervision with cardiac and electrolyte monitoring; it says nothing in favour of the crude mineral taken by mouth.

Single-arm pilot study of intravenous arsenic trioxide in 12 patients with relapsed acute promyelocytic leukaemia; 11 achieved complete remission, with degradation of the PML-RARA protein demonstrated in patient cells. This is the report that carried arsenic from Chinese hospital practice into international haematology, and it also documents the adverse profile, including QT prolongation and a leucocytosis resembling the retinoic acid syndrome.

Chinese single-arm series of 15 patients with relapsed acute promyelocytic leukaemia treated with intravenous arsenic trioxide, of whom 14 achieved complete remission, with pharmacokinetic measurement of plasma arsenic. Toxicity was described as mild at the doses used, but the report concerns a purified 0.1 percent aqueous arsenic trioxide solution infused in hospital, not an orally dosed mineral.

Review of clinical data and serial electrocardiograms from 99 patients who received 170 courses of arsenic trioxide in phase 1 and phase 2 studies. QT prolongation developed in 38 patients, with 26 reaching a QTc of 500 ms or more, and the effect was dose-related and reversible between courses. This is the primary human evidence for the cardiac hazard of absorbed arsenite and the reason arsenic therapy requires ECG and electrolyte monitoring.

Single-institution analysis of patients receiving arsenic trioxide under a protocol of aggressive electrolyte repletion and serial ECGs. QTc exceeded 500 ms in a substantial minority of patients, but with monitoring and potassium and magnesium correction no episodes of torsade de pointes or arsenic-attributed cardiac death occurred, and treatment rarely had to be stopped. The finding is that the hazard is manageable only where monitoring exists.

Two toxicologically confirmed cases of systemic heavy-metal poisoning from mucocutaneous rather than oral use of Chinese mineral medicines. A 51-year-old man who applied a hong-dan mixture containing lead tetraoxide, arsenic and mercury into an anal fistula for two weeks developed perianal gangrene, rash, anaemia, hair loss, peripheral neuropathy and muscle atrophy, with raised urine arsenic and mercury; DMPS chelation gave only partial recovery and the neuropathy persisted four years later. The authors conclude that short-term application of these preparations to damaged or infected tissue causes serious systemic poisoning, which directly undercuts the assumption that external use of an arsenical is safe.