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

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Summary

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.

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Acknowledgments

This study was supported by research funding from Wyeth Research, Collegeville, PA. We thank the patients, their families, and the clinical personnel who participated in this study and, of Wyeth Research, Bonnie Marshall and Maria Cincotta for study management and Susan Leinbach for assistance with manuscript preparation.

Author information

Author notes

  1. Bahram Forouzesh

    Present address: Liverpool Oncology, Liverpool Hospital, Liverpool, Australia

  2. Manuel Hidalgo

    Present address: The Sydney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA

  3. Eric K. Rowinsky

    Present address: ImClone Systems Incorporated, Branchburg, NJ, USA

Authors and Affiliations

  1. Mayo Clinic, Rochester, MN, USA

    Jan C. Buckner & Charles Erlichman

  2. Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, TX, USA

    Bahram Forouzesh, Manuel Hidalgo & Eric K. Rowinsky

  3. The University of Texas Health Science Center, San Antonio, TX, USA

    Bahram Forouzesh, Manuel Hidalgo & Eric K. Rowinsky

  4. Audi Murphy Veterans Affairs Hospital, San Antonio, TX, USA

    Bahram Forouzesh

  5. Wyeth Research, Collegeville, PA, USA

    Joseph P. Boni & Gary Dukart

  6. Wyeth Research, Cambridge, MA, USA

    Anna Berkenblit

Authors
  1. Jan C. Buckner
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Corresponding author

Correspondence to Jan C. Buckner.

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Buckner, J.C., Forouzesh, B., Erlichman, C. et al. Phase I, pharmacokinetic study of temsirolimus administered orally to patients with advanced cancer. Invest New Drugs 28, 334–342 (2010). https://doi.org/10.1007/s10637-009-9257-1

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  • DOI: https://doi.org/10.1007/s10637-009-9257-1

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