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Investigational New Drugs

, Volume 26, Issue 3, pp 257–264 | Cite as

Phase II study of ispinesib in recurrent or metastatic squamous cell carcinoma of the head and neck

  • Patricia A. Tang
  • Lillian L. Siu
  • Eric X. Chen
  • Sebastien J. Hotte
  • Stephen Chia
  • James K. Schwarz
  • Gregory R. Pond
  • Caitlin Johnson
  • A. Dimitrios Colevas
  • Timothy W. Synold
  • Lakshmi S. Vasist
  • Eric Winquist
PHASE II STUDIES

Summary

Ispinesib (SB-715992) inhibits the mitotic kinesin spindle protein (KSP), a novel target for anticancer therapy. A phase II study was conducted to examine the efficacy of ispinesib in recurrent or metastatic head and neck squamous cell carcinoma (RMHNSC). Patients with up to one prior line of chemotherapy for RMHNSC were treated with ispinesib 18 mg/m2 IV over 1 hour every 21 days. Twenty-one patients were enrolled onto this study with a target stage I sample size of 19. Of 20 evaluable patients, no objective responses were seen and stable disease > 2 cycles was observed in five patients (25%). The median time to progression was 1.4 (95% CI 1.3–2.3) months, median survival was 3.5 (95% CI 2.8–7.8) months, and 1 year overall survival was 20% (95% CI 8.3–48.1%). The most frequent attributable grades III–V adverse events were neutropenia (60% of patients) and leukopenia (55%). The pharmacokinetic profile was consistent with results from phase I studies. Archival tissues (n = 14) demonstrated low to moderate KSP expression by immunohistochemistry. In addition, no pharmacodynamic changes were observed in peripheral blood mononuclear cells. We detected no antitumor activity of ispinesib in RMHNSC on this dosing schedule.

Keywords

Head and neck neoplasms hsEg5 Ispinesib Kinesin spindle protein Phase II Squamous 

Notes

Acknowledgements

This work was supported by NCI contract number N01-CM-62203, and Translational Research Initiative contract number 24XS146.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Patricia A. Tang
    • 1
  • Lillian L. Siu
    • 1
  • Eric X. Chen
    • 1
  • Sebastien J. Hotte
    • 1
  • Stephen Chia
    • 1
  • James K. Schwarz
    • 1
  • Gregory R. Pond
    • 1
  • Caitlin Johnson
    • 1
  • A. Dimitrios Colevas
    • 2
  • Timothy W. Synold
    • 3
  • Lakshmi S. Vasist
    • 4
  • Eric Winquist
    • 1
    • 5
  1. 1.Princess Margaret Phase II ConsortiumTorontoCanada
  2. 2.Division of Oncology, Department of MedicineStanford University Medical CenterStanfordUSA
  3. 3.Division of Medical Oncology, Department of Clinical and Molecular PharmacologyCity of Hope Comprehensive Cancer CenterDuarteUSA
  4. 4.Department of Clinical Pharmacokinetics/Modeling and SimulationGlaxoSmithKlineResearch Triangle ParkUSA
  5. 5.London Health Sciences CentreLondonCanada

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