Arsenic trioxide, also known aswhite arsenic,arsenic(III) oxide, orarsenious oxide, is achemical compound. Itschemical formula is As2O3. It hasarsenic andoxideions in it. The arsenic is in its +3oxidation state. It is very toxic. At very low dose it can be used to treat acute promyelocyticleukemia (APL), a type ofbloodcancer.
Arsenic trioxide is a whitesolid. It dissolves in water to make anacidic solution ofarsenious acid. It dissolves easily inbases to makearsenites. It reacts with concentratedhydrochloric acid to makearsenic trichloride. It reacts with very strongoxidizing agents to makearsenic pentoxide. It reacts withreducing agents to makearsenic orarsine. Itsublimes much easier thanmetal oxides, making it easy to separate by heating themixture.
Arsenic trioxide is rarely found as amineral. It is normally made fromorpiment orrealgar, arsenic sulfide minerals. About 50,000tons ofarsenic trioxide are made eachyear.Arsenic trioxide is made byburningarsenic in air,reactingarsenic with concentratedsulfuric acid, or the roasting ofarsenic sulfideores.
Arsenic trioxide is highlytoxic when eaten. It also can betoxic if on theskin for long amounts oftime. It affects thedigestive system when eaten.Workers exposed toarsenic trioxide fumes in their job can be poisoned as well.
It is used to make elementalarsenic. It was used as apigment (inParis green) and as a woodpreservative but wasbanned in many countries because it is so toxic.
Arsenic trioxide is used to fightacute promyelocytic leukemia (APL).[1][2]
Various forms ofarsenic were used in China for over 2000 years.[3][4]Arsenic first appeared in Western Medicine in the eighteenth century. In hematology, oralarsenic was first reported in the treatment of chronic myeloid leukemia from the 1860s to 1920s inGermany and Boston City. This treatment was phased out followingWorld War II with the development of alkylating chemotherapy and radiotherapy. Intravenous pure As2O3 solution was first used in Harbin, China in 1973[3] as discovered byZhang Tingdong and colleagues.[5]
In March 1971, Han Taiyun of the 1st Affiliated Hospital started to treat cancer patients with a formula he collected from traditional Chinese medicine doctors. It was presumably an oral formula, and contained a mixture of many ingredients, includingarsenic chemicals,mercury chloride, andcinobufagin venom toad. Later, Han Taiyun turned the formula into anintramuscular injection called "713" or "cancer spirit". For certain tumors, it worked and became a local hit. But Han Taiyun gave that treatment up because the formula was too toxic for some patients.[6]
Zhang Tingdong is a doctor ofTraditional Chinese Medicine at First Clinical Hospital, affiliated withHarbin Medical University inHarbin, a city in the far north of China. He is also a hematologist (blood specialist).[7][8]
In 1972, Zhang started to cooperate with Han Taiyun. Instead of working on many cancers, Zhang Tingdong focused mainly on leukemia. Also, instead of using a mixture of many ingredients, Zhang tested each individual component of the formula. He found that while thearsenic component is effective against leukemia, mercury chloride and cinobufagin venom toad were not, and causedrenal toxicity andhigh blood pressure respectively. Their first paper was published in 1973, attributed to Zhang Tingdong, Pengfei Zhang, Wang Shouren, Han Taiyun at the Heilongjiang medical reports. They used "cancer injection" (also called "cancer spirit No. 1" or "Ailing-1")[4][6] in the treatment of 6 cases of patients with chronic myeloid leukemia. They usedarsenic trioxide as the mainingredient, with some trace "pink powder (mercury chloride)". After the treatment, the 6 patients, including a chronic-turned-acute leukemia patient, experienced improved symptoms. They also mentioned thatarsenic trioxide is effective in treating acute leukemia.[6]
The results were initially published on Chinese-language literature. In the 1990s, Zhang began to write in English, exposing this method to a broader scientific community. His work became widely known after 1996, when he co-authored aBlood article withChen Zhu about this method.[9][10] From 1994, the therapeutic value of intravenous pure ATO for the treatment of APL were further confirmed through clinical trials with the help of researchers from Shanghai, New York, etc.[11][12] Intravenous pure As2O3 solution’s mechanism of action, pharmacokinetics and clinical efficacy of was extensively published[3] and was later approved for leukemia treatment in the United States in 2000.[13]
The development of pure oralarsenic trioxide was invented and patented in Hong Kong, China. With memories of the Fowler’s solution, an oral As2O3 formulation or the “modern” liquor arsenicalis was revived.[3] Oralarsenic trioxide was first used in theQueen Mary Hospital (QMH) to treatleukemia in the late 1940s and early 1950s. Its use was discontinued for almost half a century until 1998. That year, researchers at the QMH began to study the use of oralarsenic again. To figure out the safety and dosage, the team first checked the old medical records available from theHong Kong Medical Museum. After two years of research, an oral formulation ofarsenic was successfully developed and was granted a US patent[14] in 2009.[15][16] Oral preparation of As2O3 (oral-As2O3) was shown to be efficacious for APL in first relapse (R1), inducing second complete remission (CR2) in more than 90% of patients. Further, in an effort to prevent relapses, oral-As2O3 was used during induction and maintenance of CR1. This strategy resulted in favorable overall-survival (OS) and leukemia-free-survival (LFS). This 1 mg/ml oral-As2O3 solution has a bioavailability comparable with that of i.v. As2O3.[3]
Oralarsenic trioxide (Oral-ATO; ARSENOL®) from Hong Kong was also the first oral preparation of purearsenic trioxide produced under the Good Manufacturing Practice (GMP) standards.[3] The formulation was developed by ProfessorKwong Yok Lam and colleagues from theUniversity of Hong Kong.[17] As of 2024, only Hong Kong uses oralarsenic to combat relapsed APL. Intravenousarsenic trioxide is used in other parts of the world. The disadvantages of intravenousarsenic trioxide treatment includes high cost (around US$50,000 dollars per month, not including the high hospitalization cost involved) and serious cardiac toxicity.[4] In 2025, it was reported that “Oral-ATO has obtained orphan drug designation from USFood and Drug Administration and the European Medicines Agency.”[18]
Ifarsenic poisoning occurs (with the person experiencing seizures,muscle weakness, confusion),[19] the drug should not be given anymore and appropriate treatment should be started.Penicillamine is commonly used at a dose of up to 1 g/day.[20] For patients unable to take medicine by mouth,dimercaprol can be given through muscle injection at a dose of 3 mg/kg body weight every 4 hours[21] until life-threatening symptoms become less severe. In cases ofcoagulopathy,[22]DMSA is used at a dose of 10 mg/kg body weight every 8 hours for 5 days, followed by every 12 hours for 2 weeks.[23]Kidney dialysis may also be considered.[24]
On the other hand,Realgar/Indigo naturalis formula (RIF) was developed in the 1980s entirely based ontraditional Chinese Medicine (TCM) concepts and comprises realgar, Indigo naturalis, Salvia miltiiorrhiza and Radix pseudostellariae. Tetraarsenic tetrasulphide (As4S4), indirubin and tanshinone IIA are the active ingredients of RIF with in-vitro synergism.[3] All oral, chemotherapy-free model in the frontline management of APL highlighting the applications of RIF is being developed as of 2025. A major obstacle to cure in APL is early deaths. In addition, multi-centre clinical trials in patients treated with ATRA,arsenic trioxide and anthracyclines reported a relatively low incidence of early deaths of 3-10%. There is a trend of evolution of various therapeutic approaches from hospital-based induction and consolidation to home-based oral As2O3-based therapy especially during consolidation and maintenance. Other oral formulations of As2O3 are also being investigated with the hope of eventually developing an all oral, effective regimen in standard-risk APL.[3]
Therapeutic application of intravenousarsenic trioxide is being developed inUnited Kingdom using the attenuatedarsenic trioxide regimen in newly diagnosed APL. The treatment of “high-risk” APL remains a topic of contention as As2O3 is not yet approved for this indication. An exploratory study by theMD Anderson Cancer Center using ATRA-As2O3 with or without gemtuzumab ozogamacin (GO) suggested that an essentially chemotherapy-free regimen might be feasible for the upfront treatment of APL. The role of hematopoietic stem cell transplantation (HSCT) in the current era ofarsenic trioxide was also reassessed. As2O3-based regimens are currently regarded as the first option for relapsed APL. The development of As2O3 –based therapy has improved the outcome of APL, from once the most fatal to currently the most curable leukemia.[3]
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As of 2009, animal studies have shown that the drug also affects ovarian,[25] liver,stomach,[26] prostate, and breast cancers,[27] as well asgliomas[28] andpancreatic cancer (in combination withparthenolide).[29]
Arsenic trioxide also appears promising for treating autoimmune diseases (based on studies in mice).[30]
Arsenic derivatives have been identified as compounds with therapeutic potential for over 2000 years in Greek and Chinese medicine. The first evidence of the efficacy of arsenic in leukemia was reported in 1882.(1) In the 1990s, researchers from China showed complete clinical remissions in two-thirds of patients with acute promyelocytic leukemia (APL) treated with arsenic, and a survival rate of 60% at 7 years...
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