Oral mucositis and salivary methotrexate concentration in intermediate‐dose methotrexate therapy for children with acute lymphoblastic leukemia

Abstract

The relationship between salivary methotrexate (MTX) concentration and severity of oral mucositis after administration of MTX was investigated in six children with acute lymphoblastic leukemia. They received two administrations of MTX at 500 mg/m2 with one third given bolusly and the remainder by 24-hour continuous infusion. No significant difference among patients or administration session was observed in serum MTX concentration. Detectable concentrations of salivary MTX (greater than 0.01 microM) were observed during nine of the ten infusions. A concentration of 0.1 microM or more, apparently lasting at least 12 hours, was observed during one infusion and followed by severe mucositis. During two of the ten infusions for different patients, concentrations of 0.04 to 0.07 microM and 0.02 to 0.04 microM, apparently lasting at least 12 and 18 hours, respectively, were observed, followed by moderate mucositis. During the other seven infusions, either much shorter or no increase in salivary MTX concentration was observed, with only mild or no subsequent mucositis. Analysis by Kendall's rank method showed a statistical correlation between concentration at 6 hours of infusion and severity of oral mucositis. The findings suggest that the early secretion of MTX into saliva has a significant role in the development of oral mucositis in leukemic children.

Clinical and Pharmacokinetic Risk Factors for High-dose Methotrexate-induced Toxicity in Children with Acute Lymphoblastic Leukemia: A Logistic Regression Analysis

“…Seven days after the infusion, 2% of the patients in our series had a WBC count of less than 1 ×10 9 /L. For mucositis, an incidence close to 52% has been reported in studies focusing on especially MTX-induced mucositis (20,21). The 64% incidence of reversible elevation of ALAT concentrations in the blood after HD-MTX administration is in accordance with several previous studies (19, 22 -24).…”

Xerostomia and hypofunction of the salivary glands in cancer therapy

“…Saliva-to-plasma ratios range from 0.1 to 0.5 for 5-fluorouracil in whole saliva, from 0.01 to 0.3 for methotrexate in whole saliva and from 0.09 to 0.23 for doxorubicin (which has a short elimination half-life) in parotid saliva [22,67,102,123,128]. Saliva-to-plasma ratios range from 0.1 to 0.5 for 5-fluorouracil in whole saliva, from 0.01 to 0.3 for methotrexate in whole saliva and from 0.09 to 0.23 for doxorubicin (which has a short elimination half-life) in parotid saliva [22,67,102,123,128].…”

Development and validation of a liquid chromatographic method for the simultaneous determination of four anthracyclines and their respective 13-S-dihydro metabolites in plasma and saliva

“…However, saliva is a promising matrix to predict gastrointestinal side effects (e.g. oral mucositis) of cytotoxic drugs [28,29], and could be an alternative matrix for blood sampling if saliva/plasma ratios were predictable.…”