A drug shortage led to cancer relapses in children and young adults
in 2010, a real-world consequence of the ongoing problems of drugs in
short supply in the USA, a hospital analysis showed for the first time
The finding suggests that substitutes for drugs in
short supply can pose unsuspected health risks for patients with cancer.
In this case, the generic drug, mechlorethamine, is part of a
three-month chemotherapy treatment for Hodgkin's lymphoma, a cancer of
the lymph nodes and spleen that yearly afflicts perhaps 9,000 people,
mostly teenagers nationwide.
Mechlorethamine is one of hundreds
of drugs that have been in short supply in the past three years,
according to the Food and Drug Administration. In the New England Journal of Medicine
report led by Monika Metzger of St. Jude Children's Research Hospital
in Memphis, physicians show real harm tied to the shortage of the drug
"The difference is just shocking. This had a real impact
on patients," Metzger says. "We thought the alternative was just as
safe, of course, so it was a real surprise when we reviewed the data."
shortage ended in October, according to manufacturer Lundbeck of
Deerfield, Ill., which recently sold the drug to another company.
Manufacturing facility problems triggered the shortage in 2010, forcing
physicians in the study to switch to a different generic drug regimen to
battle Hodgkin's lymphoma, one of the most treatable cancers.
hospital records to review the effects of the switch, study physicians
compared cancer relapse rates among 181 patients treated with the
original drug and 40 patients treated with a substitute after the
shortage emerged. They found that while 25% of patients on the new
regimen suffered cancer relapses, that happened to only 12% using the
original drug, a statistically significant difference. None of the
patients died, but ones whose cancer returned faced more toxic doses of
cancer drugs and bone marrow transplants, tied to heart disease and
more cancer later in life.
"This isn't the most tightly controlled
study ever conducted, but it raises real questions about safety with
all these shortages," says cancer expert Bruce Chabner of Massachusetts
General Hospital in Boston. The American Society for Health-System
Pharmacists lists 231 drugs as undergoing shortages, many of them
vaccines and generic cancer drugs. "This is a ridiculous situation for
the industry that leads the world in 21st-century meds but can't provide
1960s drugs," Chabner says. Hospitals and pharmacies are often forced
to turn to a "gray market" in resold drugs to beat shortages, he says,
wasting time and imposing higher costs on the health care system.
the quality of drugs is a key focus, we remain extremely concerned
about the current and potential shortages," says Stephanie Yao of the
Food And Drug Administration.
Last year, President Obama said
prescription drug shortages, which had tripled from 2005 to 2010, "pose a
serious and growing threat to public health." He issued an executive
order that called for reporting on shortages, speeding up review of
steps needed to alleviate them and an investigation of hoarding by
sellers. A "user fee" law reauthorized by Congress in July has
encouraged the industry to notify the agency of shortages, Yao says. The
FDA is tracking about 100 manufacturing-related drug shortages, down
from 180 at this time last year.
"We did everything we could to
minimize (the) disruption in supply," says Lundbeck spokesman Matt
Flesch, who says that starting in 2005, the company went through 20
firms in a failed attempt to hire a contractor to make the drug at a new
facility. Lundbeck announced this month that it was selling the drug
and nine others, including the leukemia drug, asparaginase, also
undergoing a shortage, for $80 million to another drugmaker.
essential fact is that generic drugs are a low-profit industry, making
it less attractive to drugmakers," Chabner says, a reality he says is
driven by federal drug cost reimbursement rates and pharmaceutical
purchasing firm practices. "Eventually, we're going to get into real
trouble unless we solve this."