Two decades ago, treatment for acute promyelocytic leukemia (APL), a cancer of the blood, was not as effective as it is today. Haematologists would often send home patients who relapsed after what was then considered the standard of care, with palliation as their only source of comfort.
The same was true at the Christian Medical College and Hospital (CMC), Vellore. However, in 1997, two patients who had relapsed and been sent home with palliation, returned six months later looking completely normal.
This piqued the interest of the haematologists at CMC, who were treating and following up on these patients. On further inquiry, they found out that both patients had travelled to Dehradun after relapsing, to see an Ayurvedic practitioner there. He had given them a treatment comprising of a combination of metals, which had miraculously appeared to cure them.**
It was known that the mixture used by the Ayurvedic practitioner contained arsenic, which was confirmed after chemical analysis. Arsenic is highly poisonous; however, it has made many appearances in medical pharmacopoeias across the world for the past two thousand years. When used in small doses, arsenic had been found to cure a variety of human ailments, from acne to syphilis (of course, the medical world has now developed far less toxic treatments).
When it comes to cancer, however, toxins are often a necessary part of treatment. Chemotherapy itself is essentially poison that is introduced into the body to kill cancer cells. Today, chemotherapy has evolved to the point where there are certain treatments that will only target cancerous cells; but as early as three decades ago, chemotherapy comprised of non-specific cytotoxins – chemicals that would destroy all cells, not just cancerous ones. Unfortunately, this was the only way to reduce the number of malignant cells in the body (this is true for most cancers even today).
Around the same time of the two APL patients’ unforeseen recovery, Chinese research was published, stating that arsenic trioxide (ATO) was highly effective in treating patients with relapsed APL.
Keeping these observations in mind, Dr. Vikram Mathews, a haematologist at CMC, Vellore, worked with the Pharmacy department of his institution to develop a pure arsenic trioxide (ATO) formulation to administer to patients who were diagnosed with APL.
Mathews and his team went on to develop a single ATO based treatment schedule for APL. Through a series of studies, he determined the short and long term efficacy and safety of both this compound and the schedule used at CMC1-3. He demonstrated that even as a single agent, ATO was more effective and less toxic than the conventionally accepted treatment for APL. Another driving force behind his research was that ATO was far more cost-effective than conventional chemotherapy, which meant that more patients would be able to access it4. In those days, the production of one vial of 10mg of ATO (a day’s dose for a patient) cost about Rs. 20.***
Today, ATO is internationally accepted to be the most effective treatment for APL, not just for patients who suffer relapses, but for newly diagnosed patients as well5. And in the case of Dr. Vikram Mathews, this breakthrough was achieved by a combination of fortuitous coincidence and perseverance, inspired from deep within the roots of ancient Indian medicine itself.
** However, patients who continued to ingest this Ayurvedic medicine for years after it was no longer required developed other health conditions associated with chronic arsenic poisoning
*** It would be of interest to note that this extremely low-cost therapy was subsequently patented in the United States, and in most Western countries where the patent is applicable, the cost of 10 mg of ATO today varies between US$400 to $6004. This brings into focus the issues surrounding patenting of such compounds and is separate topic of discussion on its own.
- Mathews V, George B, Lakshmi KM, et al. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity. Blood. 2006;107(7):2627-2632.
- Mathews V, George B, Chendamarai E, et al. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: long-term follow-up data. J Clin Oncol. 2010;28(24):3866-3871.
- Mathews V, Desire S, George B, et al. Hepatotoxicity profile of single agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia, its impact on clinical outcome and the effect of genetic polymorphisms on the incidence of hepatotoxicity. Leukemia. 2006;20(5):881-883.
- Bankar A, Korula A, Kulkarni UP, et al. Resource utilization and cost effectiveness of treating acute promyelocytic leukaemia using generic arsenic trioxide. Br J Haematol. 2020;189(2):269-278.
- Sanz MA, Fenaux P, Tallman MS, et al. Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet. Blood. 2019;133(15):1630-1643.