The effect of prior cisplatin therapy on the pharmacokinetics of high-dose methotrexate

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
W R CromW E Evans

Abstract

The pharmacokinetics of high-dose methotrexate (MTX, 5-15 g/m2) were evaluated in 11 children and adolescents who had previously received two to eight doses of cisplatin (90 mg/m2) in the treatment of malignant solid tumors. The half-life for disappearance of MTX from serum during the first 24 hours after infusion was determined from serum samples obtained at the end of a six-hour infusion and six, 12, and 24 hours after infusion. These values were compared to a mean half-life of 2.83 (+/- 0.34) hours following 489 courses administered to 71 patients who had not received cisplatin. Stepwise multiple linear regression analysis of patient variables revealed cumulative cisplatin dosage and time from last cisplatin dose as the best predictors of MTX half-life (r2 = 65.4%, p less than 0.001). The best predictors of 24-hour serum concentration were cumulative cisplatin dosage and MTX dosage (r2 = 54.2%, p less than 0.001) in the multiple linear regression model. Patients with delayed MTX clearance received additional leucovorin and experienced no severe toxicity. Patients receiving up to 270 mg/m2 of cisplatin appear to have minimal increases in MTX half-life, while the likelihood of delayed clearance increases in patients who have r...Continue Reading

Citations

Feb 6, 2020·Biopharmaceutics & Drug Disposition·Zheng-Yuan ShiDan Yan
Mar 26, 2008·Pediatric Hematology and Oncology·Parameswaran AnoopJulie Mycroft
Oct 30, 2016·Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners·Hieu X Tran, Jon D Herrington

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