Methotrexate (MTX) is an antifolate therapeutic agent that possesses potent anticancer activity against both solid tumors and leukemia.1
High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m2, is used to treat a range of adult and childhood cancers, including1:
For patients with healthy renal function, HDMTX may be safely administered with appropriate supportive care; however, despite standard support measures, HDMTX carries the risk of severe toxicity2,3:
Up to 12% of patients who receive HDMTX will experience delayed MTX clearance due to AKI.2,4-6 Delayed MTX clearance due to AKI is an oncologic emergency that can lead to potentially irreversible life-threatening systemic toxicity and organ damage.2-4,7
Patients who survive an episode of AKI have8:
The rate of cardiovascular events is as high as 22% and mortality related to cardiovascular events is 33% in patients with AKI.9
Grade 3-4 toxicities in 43 patients with delayed MTX clearance due to HDMTX-induced AKI included hematologic, renal, hepatic, and CNS toxicity as well as mucositis (all in >10% of patients). Grade 3-4 hematologic toxicity occurred in 60% of patients.10
|Toxicity||Patients, n (%)|
There are many factors associated with MTX that can increase the risk of AKI, including2,4:
|Tumor types||Incidence of AKI|
|Primary CNS lymphoma (N=154)||3-7%|
|Pediatric acute lymphoblastic leukemia (N=1286)||3.6%|
*Tumor types included acute lymphoblastic leukemia, lymphoma, CNS lymphoma germ cell tumor, and osteosarcoma.
Patients who have one or more of the following risk factors may experience delayed MTX clearance2,4,10:
BMI, body mass index; CrCl, creatinine clearance; NSAID, nonsteroidal anti-inflammatory drug; PPI, proton pump inhibitor.
It may not be possible to predict who will experience kidney injury or failure during HDMTX treatment.10 Only Voraxaze reduced plasma MTX levels by ≥97% within 15 minutes.14