OBJECTIVES: High-dose methotrexate (HDMTX) (≥1 g/m²) is widely administered to treat numerous cancers. However, delayed MTX elimination is attributed to systemic toxicities. This study aimed to explore risk factors for delayed MTX elimination.

METHODS: This is a single-center study enrolled patients who received HDMTX between July 2014 and August 2019. Plasma MTX concentrations 24 h (T24), 48h (T48), 72h (T72), and 96 h (T96) after administration were used as indices of MTX elimination. The baseline patient characteristics were collected and compared between groups with or without delayed MTX elimination. Risk factors for delayed MTX elimination were explored using stepwise logistic regression model.

RESULTS: We enrolled 165 courses of HDMTX administered to 57 patients. The incidence of delayed elimination of MTX was 37.6%, 35.1% and 48.5% in overall, adults, and pediatrics, respectively. Multivariate logistic regression revealed that male (odds ratio [OR] 3.92; P = 0.001), baseline creatinine clearance (OR 0.98; P = 0.010), diarrhea (OR 14.27; P < 0.01), acute kidney injury or delay elimination at prior cycle (OR 3.06; P = 0.006), and concurrent use of penicillin (OR 4.64; P = 0.020) were significantly associated with delayed MTX elimination.

CONCLUSIONS: Male gender, lower baseline creatinine clearance, diarrhea, acute kidney injury or delay elimination at prior cycle, and concurrent use of penicillin may increase risk of delayed MTX elimination. Knowing these factors make patients safer to receive HTMTX.