Antineoplastic agents: high-dose methotrexate and citrovorum factor rescue.
Therapeutic drug monitoring procedures after moderate and high-dose methotrexate (MTX) therapy are reviewed. Serum levels of MTX along with creatinine clearance and weight loss can serve to identify patients at risk of serious hematological toxicity. Preventive measures to avert or reduce MTX toxicity include increased citrovorum factor rescue treatment, hydration, and alkalinization of the urine in order to increase the urinary clearance of MTX and prevent its precipitation in acidic urine. The toxicity of MTX is associated with a prolonged retention of the drug in the body. Since the initial clearance of MTX correlates well with endogenous creatinine clearance, only patients with normal renal functions are eligible for high-dose MTX therapy; however, MTX-induced renal toxicity may impair renal function during the course of therapy. Therefore, careful drug monitoring techniques are essential and have contributed to the effective use of high-dose MTX, although the potential of serious toxicity cannot be completely prevented. Further studies are needed to understand the complex mechanisms by which MTX exerts its toxic and therapeutic effects in cancer patients.
D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D002955:Leucovorin / Q000627:therapeutic use*; D008727:Methotrexate / Q000009:adverse effects* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy*
D002955:Leucovorin; D008727:Methotrexate