A phase I study of the combination of temsirolimus with irinotecan for metastatic sarcoma

Claire F. Verschraegen, Sujana Movva, Yongli Ji, Berndt Schmit, Robert H. Quinn, Ben Liem, Therese Bocklage, Monte Shaheen

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

mTOR inhibitors are emerging as important anti-neoplastic agents with a wide range of clinical applications. The topoisomerase I inhibitor irinotecan is a potent DNA damaging drug, with a broad spectrum of anticancer activities. mTOR appears to enhance cancer cell survival following DNA damage, thus the inhibition of mTOR after irinotecan could theoretically show synergistic activities in patients. Both mTOR inhibitors and irinotecan have been used as single agents in soft tissue sarcomas with limited efficacy. We completed a phase I trial of the combination of the mTOR inhibitor, temsirolimus, and irinotecan in patients with advanced soft tissue sarcoma. Seventeen patients were recruited. The Phase II recommended dose is 20 mg of temsirolimus and 80 mg/m 2 of irinotecan administered on weekly basis for three out of four weeks. Most frequently encountered toxicities include cytopenias, fatigue, and gastrointestinal toxicities. Two patients (one with leiomyosarcoma and one with high grade undifferentiated sarcoma) had stable disease for more than 12 months.

Original languageEnglish (US)
Pages (from-to)418-429
Number of pages12
JournalCancers
Volume5
Issue number2
DOIs
StatePublished - Jun 2013

Keywords

  • Irinotecan
  • Phase I
  • Sarcoma
  • Temsirolimus
  • mTOR inhibitors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Verschraegen, C. F., Movva, S., Ji, Y., Schmit, B., Quinn, R. H., Liem, B., Bocklage, T., & Shaheen, M. (2013). A phase I study of the combination of temsirolimus with irinotecan for metastatic sarcoma. Cancers, 5(2), 418-429. https://doi.org/10.3390/cancers5020418