Phase i study of terameprocol in patients with recurrent high-grade glioma

Stuart A Grossman, Xiaobu Ye, David Peereboom, Myrna R. Rosenfeld, Tom Mikkelsen, Jeffrey G. Supko, Serena Desideri

Research output: Contribution to journalArticle

Abstract

Terameprocol is a global transcription inhibitor that affects cell division apoptosis, drug resistance, hypoxia responsive genes, and radiation resistance in hypoxia. A multicenter, dose-escalation study was conducted in heavily pretreated patients with recurrent, measurable, high-grade gliomas. Terameprocol was administered intravenously for 5 consecutive days each month and discontinued for toxicity or progression. Patients taking enzyme-inducing antiseizure drugs (EIASDs) were escalated independently. Thirty-five patients with a median Karnofsky performance status of 80, median age of 46 years, and median of 2 prior treatment regimens were accrued. Doses of 750, 1100, 1700, and 2200 mg/day were administered. Terameprocol was reformulated to avoid acidosis related to the excipient and was well tolerated at 1700 mg/day. Hypoxia and interstitial nephritis were noted at 2200 mg/day. Concurrent administration of EIASD did not significantly affect the serum pharmacokinetics of the terameprocol. Although no responses were seen, stable disease was noted in 9 (28) of 32 evaluable patients, with 5 (13) continuing treatment for >6 months (

Original languageEnglish (US)
Pages (from-to)511-517
Number of pages7
JournalNeuro-Oncology
Volume14
Issue number4
DOIs
StatePublished - Apr 2012

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Glioma
Karnofsky Performance Status
Interstitial Nephritis
Excipients
Enzymes
Acidosis
Drug Resistance
Pharmaceutical Preparations
Cell Division
Pharmacokinetics
Radiation
Apoptosis
terameprocol
Therapeutics
Serum
Genes
Hypoxia

Keywords

  • glioblastoma
  • high grade glioma
  • phase I trial
  • terameprocol
  • transcription inhibitor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Clinical Neurology

Cite this

Grossman, S. A., Ye, X., Peereboom, D., Rosenfeld, M. R., Mikkelsen, T., Supko, J. G., & Desideri, S. (2012). Phase i study of terameprocol in patients with recurrent high-grade glioma. Neuro-Oncology, 14(4), 511-517. https://doi.org/10.1093/neuonc/nor230

Phase i study of terameprocol in patients with recurrent high-grade glioma. / Grossman, Stuart A; Ye, Xiaobu; Peereboom, David; Rosenfeld, Myrna R.; Mikkelsen, Tom; Supko, Jeffrey G.; Desideri, Serena.

In: Neuro-Oncology, Vol. 14, No. 4, 04.2012, p. 511-517.

Research output: Contribution to journalArticle

Grossman, SA, Ye, X, Peereboom, D, Rosenfeld, MR, Mikkelsen, T, Supko, JG & Desideri, S 2012, 'Phase i study of terameprocol in patients with recurrent high-grade glioma', Neuro-Oncology, vol. 14, no. 4, pp. 511-517. https://doi.org/10.1093/neuonc/nor230
Grossman, Stuart A ; Ye, Xiaobu ; Peereboom, David ; Rosenfeld, Myrna R. ; Mikkelsen, Tom ; Supko, Jeffrey G. ; Desideri, Serena. / Phase i study of terameprocol in patients with recurrent high-grade glioma. In: Neuro-Oncology. 2012 ; Vol. 14, No. 4. pp. 511-517.
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