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Safety of delayed leucovorin “rescue” following high-dose methotrexate in children

✍ Scribed by Camitta, Bruce M. ;Holcenberg, John S.

Publisher
John Wiley and Sons
Year
1978
Tongue
English
Weight
274 KB
Volume
5
Category
Article
ISSN
0098-1532

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✦ Synopsis

High-dose methotrexate (HDMTX) with leucovorin (CF) "rescue" is being investigated for treatment of many malignant tumors. CF is usually begun 2 hours after ending the HDMTX infusion. However, since CF and methotrexate compete for the same cellular transport system, at high extracellular methotrexate concentrations it may be impossible to "rescue" cells with CF. A regimen of HDMTX with delayed leucovorin "rescue" was therefore designed. In this program, a 6-hour infusion of methotrexate (7.5 gm/m2) was followed 24 hours later by leucovorin "rescue." Nine patients with osteogenic sarcoma received 115 courses of this treatment. Toxicity was minimal. Plasma methotrexate values were identical to those following early CF 'rescue" regimens. HDMTX with delayed "rescue" is well tolerated. Although theoretically sound, further studies are needed to determine its efficacy in comparison to standard early "rescue" regimens.

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The pharmacokinetics of methotrexate (MTX), 7-hydroxymethotrexate (7-OHMTX), 2,4-diaminomethylpteroic acid (APA), folinic acid, and 5-methyltetrahydrofolate (5-MTHF) have been studied during 21 high-dose MTX (HDMTX) infusions (5 g.m-2 in 24 h) with leucovorin (LCV) rescue, a component of the therapy