Thymidine rescue of high-dose methotrexate in humans

S. B. Howell, W. D. Ensminger, A. Krishan, E. Frei

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Abstract

Thymidine rescue was administered following 63 courses of high dose methotrexate in 20 patients. In the first part of this study, the methotrexate was given as a 24-hr infusion and the dose was escalated from 0.14 to 8.54 g/sq m; in the second part, methotrexate was infused to maintain a serum concentration of 15 μM for 30, 36, or 40 hr. Thymidine rescue was started immediately after the end of the methotrexate infusions, and consisted of 8 g/sq m/day for 3 days or until serum methotrexate was below a toxic level. Mucositis and myelosuppression were the major toxicities. Neither was dose related. Serum methotrexate levels were proportional to the logarithm of the methotrexate dose. There was a mean 6-fold increase in thymidine concentration during rescue. However, thymidine levels prior to and during rescue were not related to the incidence of subsequent toxicity. Recovery of DNA synthesis in bone marrow cells was evident by nucleoside precursor incorporation at 24 hr after the start of rescue. Two of 16 evaluable patients achieved partial responses. This study indicates that thymidine is an effective rescue agent for high-dose methotrexate in humans.

Original languageEnglish
Pages (from-to)325-330
Number of pages6
JournalCancer Research
Volume38
Issue number2
StatePublished - Jan 1 1978
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Howell, S. B., Ensminger, W. D., Krishan, A., & Frei, E. (1978). Thymidine rescue of high-dose methotrexate in humans. Cancer Research, 38(2), 325-330.