Panel Sets Guidelines for Glucarpidase Use When Cancer Patients Face Toxic Side Effects
Published October 27, 2017 | The Oncologist
In children with osteosarcoma or acute lymphoblastic leukemia (ALL), standard treatment calls for a high-dose infusion of methotrexate.
In some cases, this chemotherapy can cause acute kidney injury, which impairs the body from eliminating methotrexate. When that happens, clinicians rely upon the enzyme glucarpidase to degrade the drug and stop the toxic side effects.
However, glucarpidase is rarely used, it can cost up to $25,000 per vial (most patients need two to four vials), and there have been no clear guidelines for its use. While large centers like Cincinnati Children’s stock the drug, many other pediatric hospitals do not, which means some patients can face potentially risky delays in receiving needed treatment.
Now an international team of researchers led by Cincinnati Children’s is helping to clarify when to use the drug.
“Normally, methotrexate infusions start in one afternoon and finish the next. By the time a second measurement is taken to evaluate toxicity, it can be the middle of the night when the doctor is making decisions,” says Laura Ramsey, PhD, of the Division of Clinical Pharmacology and Research in Patient Services. “Timing is crucial. If we can identify the patients who are going to need the drug within 48 hours, we can make a significant difference.”
The maker of glucarpidase provided an educational grant to create an expert panel, selected by Ramsey and Alexander Vinks, PharmD, PhD, Director of Clinical Pharmacology. Among them: study co-author Maureen O’Brien MD, MS, of the Cancer and Blood Diseases Institute.
Glucarpidase is remarkably efficient, dissipating 95 percent of methotrexate within five minutes. The question becomes when best to administer it?
The team concluded that glucarpidase may be needed if the 36-hour concentration of methotrexate exceeds 30 mM, the 42-hour concentration exceeds 10 mM, or the 48-hour concentration remains above 5 mM with significantly elevated creatinine.
