Phase 2 study of dasatinib in the treatment of head and neck squamous cell carcinoma

Authors

  • Heather D. Brooks MD,

    1. Division of Cancer Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Bonnie S. Glisson MD,

    1. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • B. Nebiyou Bekele MD,

    1. Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Lawrence E. Ginsberg MD,

    1. Department of Diagnostic Radiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Adel El-Naggar MD,

    1. Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Kirk S. Culotta MD,

    1. Department of Pharmacy-Pharmacology Research, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Naoko Takebe MD,

    1. Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
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  • John Wright MD,

    1. Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
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  • Hai T. Tran MD,

    1. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Vassiliki A. Papadimitrakopoulou MD

    Corresponding author
    1. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    • Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Unit 432, 1515 Holcombe Blvd., Houston, TX 77030
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    • Fax: (713) 792-1220

Errata

This article is corrected by:

  1. Errata: Erratum: Phase 2 study of dasatinib in the treatment of head and neck squamous cell carcinoma Volume 118, Issue 9, 2560, Article first published online: 1 September 2011

Abstract

BACKGROUND:

Treatment options for patients with advanced head and neck squamous cell carcinoma (HNSCC) are scarce. This phase 2 study was conducted to evaluate the safety, tolerability, pharmacokinetics, and efficacy of dasatinib in this setting.

METHODS:

Patients with recurrent and/or metastatic HNSCC after platinum-based therapy were treated with dasatinib either orally or via percutaneous feeding gastrostomy (PFG). Primary endpoints were 12-week progression-free survival (PFS) and objective response rate with a 2-stage design and early withdrawal if the 12-week PFS rate was ≤20% and no patients had an objective response (OR). Forty-nine serum cytokines and angiogenic factors (CAFs) were analyzed from treated patients.

RESULTS:

Of the 15 patients enrolled, 12 were evaluable for response, and all patients were evaluable for toxicity. No OR was observed and 2 patients (16.7%) had stable disease (SD) at 8 weeks. The median treatment duration was 59 days, the median time to disease progression was 3.9 weeks, and the median survival was 26 weeks. One patient required a dose reduction, 3 patients required dose interruptions, and 4 patients were hospitalized for toxicity. Dasatinib inhibited c-Src both when administered orally and via PFG. Greater mean drug exposure, decreased half-life, and greater maximum concentration were observed in patients receiving dasatinib via PFG. Eleven baseline CAFs were associated with treatment outcome and 1 CAF, macrophage migration inhibitory factor, was found to be differentially modulated in correlation with SD versus disease progression.

CONCLUSIONS:

Single-agent dasatinib failed to demonstrate significant activity in patients with advanced HNSCC, despite c-Src inhibition. The toxicity profile was consistent with that reported in other solid tumors, and the drug can be given via PFG tube. Cancer 2011. © 2010 American Cancer Society.

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