Methotrexate removal during haemodialysis in a patient with advanced laryngeal carcinoma

Abstract

A 62-year-old patient on long-term haemodialysis who developed an inoperable T2N3Mo squamous-cell carcinoma of the larynx was treated with weekly low-dose methotrexate (MTX) after failing to respond to radiotherapy. The patient was initially given one dose of 10 mg MTX (6 mg/m2) as a 1-h infusion, then he received three further i.v. doses of 20 mg (12 mg/m2). Haemodialysis was performed 15-18 h after each dose and the patient received folinic acid (30 mg i.v.q 6 h) until the MTX concentration was < 0.1 mumol/l. The MTX concentration was measured regularly until it reached < 0.1 mumol/l, and additional samples were withdrawn pre- and post-dialysis. The MTX elimination rate constant and half-life were estimated with the patient on and off dialysis. The patient failed to respond to treatment but did not experience MTX-related toxicity. The elimination half-life ranged from 22 to 42 h when he was off dialysis but fell to a median of 5.5 h during dialysis. Low-dose MTX was given to a patient on regular haemodialysis without evidence of toxicity. The rate of MTX elimination was increased during haemodialysis, although high MTX concentrations persisted for several days and prolonged rescue with folinic acid was required.

Effective removal of methotrexate by high-flux hemodialysis

“…Modern protocols and institution of therapeutic drug monitoring have decreased the likelihood of these events, but in such cases, the management of delayed MTX clearance is of great importance. Previous reports have documented MTX clearance with various levels of success using HD [8,9,10,11], HD with charcoal hemoperfusion [12,13,14], HD with serum exchange [15], HD with plasma perfusion [16], and hemofiltration with plasma perfusion over an anion exchange resin [17]. In our experience, HD was superior to HD with charcoal hemoperfusion [18].…”

Systemic anticancer therapy in gynecological cancer patients with renal dysfunction

“…The use of low‐dose methotrexate was studied in hemodialysis patient in two case reports (100,101) . In the first report (101) , methotrexate was administered to a laryngeal carcinoma patient at 6–10 mg/m 2 over a 1‐h infusion weekly. A 4‐h hemodialysis was started 15–18 h after the chemotherapy and repeated 48 h later.…”

“…The elimination t 1/2 were 22–24 h and 5.5 h with dialysis off and on, respectively. There was no methotrexate‐related toxicity (101) . Another case report also showed that methotrexate at a total dose of 20 mg with leucovorin was safely administered to a patient on regular dialysis (100) .…”

“…Another case report also showed that methotrexate at a total dose of 20 mg with leucovorin was safely administered to a patient on regular dialysis (100) . Monitoring of methotrexate concentration is crucial for the use of methotrexate in such high‐risk patients (100,101) . Hemodialysis was effective in removing methotrexate in those two reports and in rescue therapy from methotrexate intoxication (102) .…”

The utility of online haemodiafiltration in methotrexate poisoning

“…Despite these precautions, the risk of renal impairment after high-dose MTX is still approximately 2% 12. The utility of HD in MTX toxicity has been reported previously, but with variable degrees 3 13. It has been shown that acute intermittent high-flux HD is an effective method of clearing high MTX levels in chronic dialysis patients on high-dose MTX treatment 3.…”