A national drug shortage has been linked to a higher rate of relapse among children, teenagers, and young adults with Hodgkin lymphoma enrolled in a national clinical trial.
In recent years, many patients and caregivers have had their medical care complicated by drug shortages, primarily of generic injectable drugs, such as 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.
Estimated 2-year cancer-free survival decreased from 88% to 75% after cyclophosphamide was substituted for mechlorethamine in the treatment of intermediate- or high-risk Hodgkin lymphoma among patients enrolled in the study, which began before the drug shortages started. The change occurred after a mechlorethamine shortage that 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.
This analysis compared how patients in each group were faring 2 years after their cancer diagnoses. It provides the first evidence of a drug shortage adversely impacting treatment outcomes in a specific patient population.
“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 years, and half were 14 years or younger.
“This is a devastating example of how drug shortages affect patients and why these shortages must be prevented,” said Monika Metzger, MD, 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.”
The senior author of the new report, Michael Link, MD, said, “Past shortages have been resolved in a variety of ways and always before a drug substitution became necessary.” Link is a professor of pediatrics in hematology-oncology at Stanford, a member of the pediatric hematology-oncology service at Packard Children’s Hospital, and immediate past president of the American Society of Clinical Oncology. “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.”
This article was published in the New England Journal of Medicine (2012; doi:10.1056/NEJMp1212468).