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A phase I and pharmacology study of continuous‐infusion low‐dose methotrexate administration
Author(s) -
Lokich Jacob J.,
Curt Gregory
Publication year - 1985
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19851115)56:10<2391::aid-cncr2820561008>3.0.co;2-w
Subject(s) - medicine , leukopenia , methotrexate , bolus (digestion) , stomatitis , pharmacology , continuous infusion , toxicity , pharmacokinetics , urology , anesthesia
Continuous intravenous infusion of methotrexate (MTX) was evaluated in a Phase I study designed to establish the optimal dose rate to provide a minimum of 28 days of constant 24‐hour drug exposure. Twenty‐six courses were administered to 21 patients at dose rates of 0.75 mg/M 2 /day to 3 mg/M 2 /day. Dose‐limiting toxicity was predominantly stomatitis at the highest dose rates. Thrombocytopenia (platelet count <100,000) without leukopenia developed in 8 of 26 courses at the lower dose rates, with or without stomatitis, and was rapidly reversible. Serial blood levels revealed detectable serum MTX concentrations at all dose rates delivered with mean MTX concentrations varying from 12.8 nM at 0.75 mg/M 2 /day to 140 nM at 2.5 mg/M 2 /day. Total‐body clearance of MTX approximated renal creatinine clearance. The recommended dose rate for continuous infusion of methotrexate is 0.75 mg/M 2 /day for 28 days, and for shorter durations (≤14 days), the optimal dose rate is 1.5 mg/M 2 /day. The continuous‐infusion schedule for MTX, therefore, results in a substantial decrease in the delivered dose compared with that achieved with a bolus schedule.