It killed Chinese emperor Guangxu a century ago and Napoleon Bonaparte’s hair was found with high levels of it. Now, the ancient poison arsenic has found a more promising use: as a children’s cancer treatment.
For the first time, arsenic trioxide is being used in a clinical trial as the first drug doctors reach for when treating kids with acute promyelocytic leukemia, a bone marrow cancer – in a discovery that seems at odds with the compound’s reputation as a deadly killer.
“We think about arsenic as a poison but the standard chemotherapy drugs we’ve had for 30 years are worse poisons,” said Wilson Miller, professor of medicine and oncology at McGill University, who has done a lot of research into arsenic.
The North American study, which includes six Canadian hospitals in five provinces, is trying to determine whether children’s cancer treatment can be made less toxic by giving arsenic upfront and reduce the chemotherapy dose – a startling approach, given that the compound has long been associated with causing cancer.
Ben Netten, a cherubic-faced seven-year-old with a toothless grin, was diagnosed with the rare leukemia last fall and became the first – and so far only – Canadian child to be enrolled in the study.
His parents said the treatment protocol he is undergoing at Children’s Hospital of Eastern Ontario in Ottawa has the best chance of putting their son’s cancer into complete remission, while reducing long-term side effects, particularly to the heart.
“During most of the arsenic treatment, Ben felt well enough to enjoy the plethora of video games at CHEO, play with his sisters at home in the evenings, and skated once a week,” mother Shirley Netten said. “And, at the end of the cycle, he was able to ski a couple of runs and swim, three days in a row.”
As part of his treatment, he was also given standard chemotherapy drugs, which have spawned periods of sheer misery. Arsenic, as it turned out, was less harsh on his system.
Study chair John J. Gregory said even though current treatment for the disease is highly effective – with 80 to 90 per cent of children having no sign of the disease five years after diagnosis – he wanted to see whether those good outcomes could be maintained, while reducing long-term side effects.
“With kids, we worry even more, because they live a long life,” said Dr. Gregory, assistant professor of pediatrics at University of Medicine and Dentistry of New Jersey. “We also worry – especially in the young kids, who still have a growing, developing heart – whether it [anthracycline chemotherapy] is more toxic.”
Jacqueline Halton, chief of pediatric division of hematology/oncology at CHEO, said she has seen children be treated successfully for all types of cancer, only to go on years later and suffer heart problems.
“I have seen children die from cardiac failure,” said Dr. Halton. “That is why it’s important we try and minimize toxicity.”
The disease is relatively rare, with only a handful of Canadian children diagnosed with it each year. Sheila Weitzman, Hospital for Sick Children’s associate director of clinical services for hematology/oncology and section head of leukemia/lymphoma, said her institution sees one case every year or two.
“The whole treatment of APL has been extremely exciting,” said Dr. Weitzman. “This used to be the worst of the leukemias.”
Stefannie Roman, of Cambridge, Ont., had arsenic treatment in 2006 after a relapse, at the age of 14.
“It was the only drug I didn’t feel sick on,” said Ms. Roman, now 18 of Cambridge, Ont. Four years after arsenic treatment, she is clear of cancer.
Steffanie Roman, 18 poses in her Cambridge, Ont., home in March 2010. She was treated in 2006 with arsenic after a recurrence of cancer.— J.P. Moczulski/The Globe and Mail
I didn’t lose my hair, I didn’t have bad headaches. I feel great; I feel just like I did before. — Stefannie Roman
As part of the clinical trial, patients are treated with arsenic upfront in six children’s hospitals in British Columbia, Manitoba, Ontario, Quebec and Nova Scotia. They are also given all-trans retinoic acid – vitamin A in its acid form – and about 40 per cent less chemotherapy.
Currently, arsenic can only be obtained through Health Canada’s Special Access Program, where 168 requests for it were made from 2006 to 2009, according to spokeswoman Christelle Legault. The program is available so those with serious or life-threatening conditions can obtain drugs – typically those that are unlicensed under certain circumstances.
Mark Minden, medical oncologist and senior scientist at Princess Margaret Hospital and the Ontario Cancer Institute, has also used arsenic on patients and called the cost – at $23,000 for a course of treatment per patient – “very outrageous.” In B.C., the therapy – 28-day or 42-day – costs $10,700 and $15,300, respectively, said Susan O’Reilly, vice-president of cancer care for the BC Cancer Agency.
“This has been around for ages,” said Dr. Minden. “We’ve actually been looking to see if we can bring the Chinese product in.”
