Investigational New Drugs

, Volume 28, Issue 3, pp 334–342 | Cite as

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
PHASE I STUDIES

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.

Keywords

mTOR Targeted chemotherapy Pharmacokinetics Phase I 

Notes

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.

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Jan C. Buckner
    • 1
  • Bahram Forouzesh
    • 2
    • 3
    • 4
    • 7
  • Charles Erlichman
    • 1
  • Manuel Hidalgo
    • 2
    • 3
    • 8
  • Joseph P. Boni
    • 5
  • Gary Dukart
    • 5
  • Anna Berkenblit
    • 6
  • Eric K. Rowinsky
    • 2
    • 3
    • 9
  1. 1.Mayo ClinicRochesterUSA
  2. 2.Institute for Drug DevelopmentCancer Therapy and Research CenterSan AntonioUSA
  3. 3.The University of Texas Health Science CenterSan AntonioUSA
  4. 4.Audi Murphy Veterans Affairs HospitalSan AntonioUSA
  5. 5.Wyeth ResearchCollegevilleUSA
  6. 6.Wyeth ResearchCambridgeUSA
  7. 7.Liverpool Oncology, Liverpool HospitalLiverpoolAustralia
  8. 8.The Sydney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimoreUSA
  9. 9.ImClone Systems IncorporatedBranchburgUSA

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