While the U.S. spends a lot of money on health care, there is little incentive to produce older drugs with small profit margins.  In addition to the financial aspects, there are many other factors involved including the following:  limited number of manufacturers, increased worldwide demand, aging production plants, shortages of materials, stockpiling, and regulatory demands. This is resulting in detrimental outcomes (NEJM 2012; 367: 2461-63).

A specific example is the shortage of mechlorethamine (nitrogen mustard).  Since the 1960s it has been part of a MOPP regimen for Hodgkin’s lymphoma.  For pediatric patients, a modification of this regimen, the Stanford V regimen, has had good success rates for Hodgkin’s lymphoma.

Due to the shortage of mechlorethamine, cyclophosphamide has been substituted into the regimen.  While this substitution was thought to be equally efficacious, a group of investigators from St. Jude/Univ Tennessee, Dana-Farber/Boston Children’s, and Lucile Packard Children’s/Stanford have found that this substitution has resulted in a much lower 2-year event-free survival: 75% with new regimen compared with 88% with previous regimen.  This is despite the fact that patients receiving the newer regimen did not have a more unfavorable treatment profile.

Patients who relapsed had salvage therapy with stem-cell transplantation.  The long-term outcome of the newer regimen group, nevertheless, appears substantially worsened.

This example is not isolated.  Other cancer-drug shortages have included cytarabine, daunorubicin, and methotrexate.  While some of these shortages have been resolved quickly, the frequency of these shortages as well as drugs used for multiple other diseases is alarming.  When physicians and pateints are faced with the prospect of receiving inferior care due to drug shortage, this is extremely “hard to swallow.”