Relapse Through Drug Shortage

Photo: Drugs in the USA

Young cancer patients in the USA suffered a
relapse due to a drug shortage during their
treatment; © panthermedia.net/Vedran Vukoja

Estimated two-year cancer-free survival for patients enrolled in the study fell from 88 to 75 percent after the drug cyclophosphamide was substituted for mechlorethamine for treatment of patients with intermediate- or high-risk Hodgkin lymphoma. The study was launched before the drug shortages began. The change occurred after a mechlorethamine shortage began in 2009. No study patients have died, but those who relapsed received additional intensive therapy that is associated with higher odds for infertility and other health problems later.

In recent years, many patients and caregivers have had their medical care complicated by drug shortages, primarily of generic injectable drugs like mechlorethamine. Mechlorethamine, which has been used in cancer treatment since the 1960s, has only recently become available again. Cyclophosphamide has been widely used in treatment of both adults and children with Hodgkin lymphoma. Based on earlier studies, the drug was considered a safe and effective alternative to mechlorethamine.

"This is a devastating example of how drug shortages affect patients and why these shortages must be prevented," said medical doctor Monika Metzger, an associate member of the St. Jude Department of Oncology and the study's principal investigator. "Our results demonstrate that, for many chemotherapy drugs, there are no adequate substitute drugs available." Past shortages have been resolved in a variety of ways and always before a drug substitution became necessary, said medical doctor Michael Link, the senior author of the new report.

"This puts a face on the problem of drug shortages and shows that the problem is real, not theoretical. This is about a curative therapy that we were unable to administer because the drug we needed was not available," Link said. "Despite heroic efforts by the drug shortage office of the Food and Drug Administration to solve the shortages of a number of medically necessary drugs, it is clear that patients are still suffering from the unavailability of life-saving drugs. A more systematic solution to the problem is needed."

Outcomes for cancer patients are often measured in terms of cancer-free survival, which is the number of years patients remain free of the disease. When researchers assessed the impact of the drug substitution, they found that estimated disease-free survival was 88 percent for the 181 patients whose treatment included mechlorethamine. It was 75 percent for the 40 patients who received cyclophosphamide instead. The difference led researchers to stop enrolling new patients in the trials.

"We can think of no credible explanation for this dramatic difference in event-free survival other than the drug substitution," the researchers noted. The analysis found that, as a group, patients who received cyclophosphamide had fewer unfavorable symptoms and were more likely to have intermediate-risk, rather than high-risk Hodgkin lymphoma. The patients ranged in age from 3 to 21. Half were age 14 or younger.

MEDICA.de; Source: Stanford University Medical Center