Phase I, pharmacokinetic study of temsirolimus administered orally to patients with advanced cancer

Jan C. Buckner, Bahram Forouzesh, Charles Erlichman, Manuel Hidalgo, Joseph P. Boni, Gary Dukart, Anna Berkenblit, Eric K. Rowinsky

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

An oral formulation of temsirolimus (Torisel®), an inhibitor of the mammalian target of rapamycin, was evaluated on an intermittent schedule (once daily for 5 days every 2 weeks) in patients with advanced cancer. The maximum tolerated dose was determined to be 75 mg after dose-limiting toxicities of grade 3 elevated aminotransferases (1 patient) and grade 3 rash (1 patient) occurred with a 100-mg dose. The most common temsirolimus-related adverse events were mucositis, rash/maculopapular rash, and asthenia. Six of 12 patients who received the 75-mg dose required dose reductions due to temsirolimus-related adverse events. Two patients who received 75-mg temsirolimus and did not have dose reductions had minor tumor responses. Relative exposure from contributions of both temsirolimus and sirolimus, the principal metabolite, was 17.9% of the 75-mg dose. Thus, oral temsirolimus, 75 mg administered once daily for 5 days every 2 weeks, was further evaluated in patients with metastatic breast cancer.

Original languageEnglish (US)
Pages (from-to)334-342
Number of pages9
JournalInvestigational New Drugs
Volume28
Issue number3
DOIs
StatePublished - Jun 1 2010

Keywords

  • MTOR
  • Pharmacokinetics
  • Phase I
  • Targeted chemotherapy

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

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    Buckner, J. C., Forouzesh, B., Erlichman, C., Hidalgo, M., Boni, J. P., Dukart, G., Berkenblit, A., & Rowinsky, E. K. (2010). Phase I, pharmacokinetic study of temsirolimus administered orally to patients with advanced cancer. Investigational New Drugs, 28(3), 334-342. https://doi.org/10.1007/s10637-009-9257-1