Updated on 27 December 2012
St Jude Children's Research Hospital study - Shortage of cyclophosphamide led to relapse of Hodgkin lymphoma
Singapore: Drug shortage is linked to higher rate of relapse among children, teenagers and young adults with Hodgkin lymphoma enrolled in a national clinical trial, according to research led by St Jude Children's Research Hospital.
The Pediatric Hodgkin Consortium, in 2002 the five institutions involved in this study adopted a seven-drug chemotherapy regimen that included mechlorethamine for the treatment of high-risk pediatric patients. The goal was to preserve high cure rates, but to reduce the risk of second cancers, infertility and other problems associated with the earlier treatments.
The strategy involved 12 weeks of the seven-drug chemotherapy regimen. Patients also received radiotherapy with the dose based on their response to chemotherapy. When mechlorethamine became unavailable, the protocol was revised to allow the cyclophosphamide substitution.
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 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. 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 Ms 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."