Abby Alonzo was eight weeks into treatment for Hodgkin lymphoma and doing great when her doctor informed the 9-year-old's parents that one ingredient in the cocktail of chemo drugs she was receiving was no longer available, and they would have to use a substitution.
"It's scary, and I was alarmed but I didn't really have a sense of how critical this drug was," said Katie Alonzo, Abby's mother. "When something like this happens, you have to put your faith in the doctors."
But by 12 weeks into treatment, Abby relapsed. Rather than receiving a planned break from treatment, she was rushed into emergency "salvage therapy," which involved more chemo, a bone marrow transplant and radiation.
The doctors at St. Jude Children's Research Hospital in Memphis, Tenn., who treated Abby, attribute her relapse to the shortage of the drug mechlorethamine, also known as nitrogen mustard. In today's New England Journal of Medicine, the St. Jude doctors, along with colleagues from the Dana-Farber cancer institute in Boston and the Lucile Packard Children's Hospital in Stanford, Calif., highlight how the scarcity of this medication has been linked to a higher rate of relapse among children, teenagers and young adults with Hodgkin lymphoma.
The 40 patients in the study who received the substitute drug cyclophosphamide experienced complications at about twice the rate of the 181 patients studied who didn't have to switch drugs. This is the first randomized study to compare the differences in treatment outcomes between the two medications.
None of the patients died, but the authors emphasize that they're only 18 months out from treatment and could still be hit with adverse effects.
"It's too soon to know about problems and success rates," said Dr. Michael Link, one of the lead investigators and a Stanford University pediatric oncologist. "Even if they're cured, they underwent intensive treatment they would have otherwise avoided and this puts them at greater risk for long-term effects such as infertility and secondary cancers."
Similar but Not the Same
Dr. Amy Billet, a pediatric oncologist at Dana-Farber who was also part of the study, said it's not possible to say beyond a shadow of a doubt that the drug swap was responsible for the higher rate of relapse, but she and her fellow investigators could think of no other credible explanation.
"You can never know what happened to one individual patient. You can only say there is an increase risk in the group who got the substitution drug," she said.
According to Link, this latest study only confirms what doctors have suspected for years: swapping one drug for another, even when the two are similar, isn't always ideal.
"We thought this one was a no-brainer because the drugs were so alike, but we discovered to our dismay that the substitution didn't work as well. This takes the problem out of the hypothetical and we can point our finger at exactly which patients suffered as a result of the shortage," he said.
A Larger Problem
Two years ago, Dr. Richard Besser and the ABC News Medical Unit embarked on a series of reports spotlighting critical shortages of drugs commonly used to treat cancer. While almost 80 percent of children with cancer can be cured with current therapies, they found that many common treatment regimens rely on older drugs – mechlorethamine has been used since the 1960s -- and some drugs have been in short supply in recent years.