Prolonged accumulation of high-dose methotrexate in a case with large liver cysts

• Published in: Cancer chemotherapy and pharmacology Vol. 64; no. 3; pp. 619 - 622
• Main Authors: Kawakami, Manabu, Omori, Hiroki, Yamagami, Tamotsu, Soma, Toshihiro
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.07.2009; Springer; Springer Nature B.V
• Subjects: Anorexia - chemically induced; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - pharmacokinetics; Antineoplastic agents; Biological and medical sciences; Burkitt Lymphoma - drug therapy; Burkitt Lymphoma - physiopathology; Cancer Research; Cysts - pathology; Diarrhea - chemically induced; Dose-Response Relationship, Drug; Humans; Liver - pathology; Male; Medical sciences; Medicine; Medicine & Public Health; Methotrexate - administration & dosage; Methotrexate - adverse effects; Methotrexate - pharmacokinetics; Middle Aged; Neutropenia - chemically induced; Oncology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Short Communication; Time Factors; Tissue Distribution; Methotrexate; Delayed clearance; Large liver cyst; Accumulation; Antineoplastic agent; Digestive system; Liver; Clearance; Antifolate; Antimetabolic; Cyst; Benign neoplasm; Pharmacokinetics; High dose; Prolonged
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-009-0982-0

Methotrexate (MTX) has been documented to accumulate in “third spaces’’ such as pleural effusions or ascitic fluids, resulting in delayed clearance and severe toxicity. We present a case of Burkitt lymphoma possessing large liver cysts, up to the size of 7 × 7 cm, wherein clearance of high-dose MTX was severely delayed, despite normal renal and liver functions. The serum MTX concentration was higher than 0.1 μM on day 12 and remained at toxic levels, higher than 0.01 μM, even on day 25, resulting in severe neutropenia, anorexia, and diarrhea. It was presumed that MTX accumulated in the liver cysts over time and was slowly released back into the serum, resulting into prolonged high serum MTX concentrations. High dose of MTX in patients with large liver cysts induces severe toxicity by virtue of MTX accumulation in the cysts and its subsequent delayed clearance.