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A phase I study evaluating the role of the anti-epidermal growth factor receptor (EGFR) antibody cetuximab as a radiosensitizer with chemoradiation for locally advanced pancreatic cancer

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Abstract

Purpose

(1) To determine the safety of the epidermal growth factor receptor (EGFR) antibody cetuximab with concurrent gemcitabine and abdominal radiation in the treatment of patients with locally advanced adenocarcinoma of the pancreas. (2) To evaluate the feasibility of pancreatic cancer cell epithelial–mesenchymal transition (EMT) molecular profiling as a potential predictor of response to anti-EGFR treatment.

Methods

Patients with non-metastatic, locally advanced pancreatic cancer were treated in this dose escalation study with gemcitabine (0–300 mg/m2/week) given concurrently with cetuximab (400 mg/m2 loading dose, 250 mg/m2 weekly maintenance dose) and abdominal irradiation (50.4 Gy). Expression of E-cadherin and vimentin was assessed by immunohistochemistry in diagnostic endoscopic ultrasound fine-needle aspiration (EUS-FNA) specimens.

Results

Sixteen patients were enrolled in 4 treatment cohorts with escalating doses of gemcitabine. Incidence of grade 1–2 adverse events was 96%, and incidence of 3–4 adverse events was 9%. There were no treatment-related mortalities. Two patients who exhibited favorable treatment response underwent surgical exploration and were intraoperatively confirmed to have unresectable tumors. Median overall survival was 10.5 months. Pancreatic cancer cell expression of E-cadherin and vimentin was successfully determined in EUS-FNA specimens from 4 patients.

Conclusions

Cetuximab can be safely administered with abdominal radiation and concurrent gemcitabine (up to 300 mg/m2/week) in patients with locally advanced adenocarcinoma of the pancreas. This combined therapy modality exhibited limited activity. Diagnostic EUS-FNA specimens could be analyzed for molecular markers of EMT in a minority of patients with pancreatic cancer.

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Acknowledgments

This study was funded by grant NIH P20 CA10195 and sponsored by the National Cancer Institute and Bristol-Myers Squibb Laboratories (New York, New York).

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Authors and Affiliations

  1. Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA

    J. P. Arnoletti, A. Frolov & J. Christein

  2. Department of Gastroenterology, University of Alabama at Birmingham, Birmingham, AL, USA

    M. Eloubeidi & S. Varadarajulu

  3. Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, USA

    K. Keene & D. J. Buchsbaum

  4. Department of Medical Oncology, University of Alabama at Birmingham, Birmingham, AL, USA

    J. Posey & T. Wood

  5. Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, 55455, USA

    Edward Greeno

  6. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA

    N. Jhala

  7. Department of Radiation Oncology, East Carolina University, Green Ville, NC, USA

    S. Russo

  8. Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA

    R. Oster

  9. Surgery Department, University of Minnesota, 420 Delaware Street SE, Mayo Mail Code 195, Minneapolis, MN, 55455, USA

    S. M. Vickers

Authors
  1. J. P. Arnoletti
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  2. A. Frolov
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  3. M. Eloubeidi
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  4. K. Keene
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  6. T. Wood
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  7. Edward Greeno
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  8. N. Jhala
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  9. S. Varadarajulu
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  10. S. Russo
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  11. J. Christein
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  12. R. Oster
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  13. D. J. Buchsbaum
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  14. S. M. Vickers
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Corresponding author

Correspondence to S. M. Vickers.

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Arnoletti, J.P., Frolov, A., Eloubeidi, M. et al. A phase I study evaluating the role of the anti-epidermal growth factor receptor (EGFR) antibody cetuximab as a radiosensitizer with chemoradiation for locally advanced pancreatic cancer. Cancer Chemother Pharmacol 67, 891–897 (2011). https://doi.org/10.1007/s00280-010-1383-0

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  • DOI: https://doi.org/10.1007/s00280-010-1383-0

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