By Dan Vergano, USA TODAY
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 Wednesday.
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 in 2010.
"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."
The shortage ended in October, according to manufacturer Lundbeck of Deerfield, Ill., which recently sold the drug to another firm. 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.
Using 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.
"While 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.
"The 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."