Neoadjuvant cetuximab, twice-weekly gemcitabine, and intensity-modulated radiotherapy (IMRT) in patients with pancreatic adenocarcinoma

J. M. Pipas, B. I. Zaki, M. M. Mcgowan, M. J. Tsapakos, G. H. Ripple, A. A. Suriawinata, G. J. Tsongalis, T. A. Colacchio, S. R. Gordon, J. E. Sutton, A. Srivastava, K. D. Smith, T. B. Gardner, M. Korc, T. H. Davis, M. Preis, S. M. Tarczewski, T. A. Mackenzie, R. J. Barth

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Abstract

Background: Neoadjuvant therapy has been investigated for localized and locally advanced pancreatic ductal adenocarcinoma (PDAC) but no standard of care exists. Combination cetuximab/gemcitabine/radiotherapy demonstrates encouraging preclinical activity in PDAC. We investigated cetuximab with twice-weekly gemcitabine and intensity-modulated radiotherapy (IMRT) as neoadjuvant therapy in patients with localized or locally advanced PDAC. Experimental design: Treatment consisted of cetuximab load at 400 mg/m.2 followed by cetuximab 250 mg/m.2 weekly and gemcitabine 50 mg/m.2 twice-weekly given concurrently with IMRT to 54 Gy. Following therapy, patients were considered for resection. Results: Thirty-seven patients were enrolled with 33 assessable for response. Ten patients (30%) manifested partial response and 20 (61%) manifested stable disease by RECIST. Twenty-five patients (76%) underwent resection, including 18/23 previously borderline and 3/6 previously unresectable tumors. Twenty-three (92%) of these had negative surgical margins. Pathology revealed that 24% of resected tumors had grade III/IV tumor kill, including two pathological complete responses (8%). Median survival was 24.3 months in resected patients. Outcome did not vary by epidermal growth factor receptor status. Conclusions: Neoadjuvant therapy with cetuximab/gemcitabine/IMRT is tolerable and active in PDAC. Margin-negative resection rates are high and some locally advanced tumors can be downstaged to allow for complete resection with encouraging survival. Pathological complete responses can occur. This combination warrants further investigation.

Original languageEnglish (US)
Article numbermds109
Pages (from-to)2820-2827
Number of pages8
JournalAnnals of Oncology
Volume23
Issue number11
DOIs
StatePublished - Nov 1 2012

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gemcitabine
Intensity-Modulated Radiotherapy
Adenocarcinoma
Neoadjuvant Therapy
Neoplasms
Survival
Standard of Care
Epidermal Growth Factor Receptor
Cetuximab
Research Design
Radiotherapy
Pathology

Keywords

  • Cetuximab
  • Gemcitabine
  • Intensity-modulated radiotherapy
  • Neoadjuvant therapy
  • Pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Pipas, J. M., Zaki, B. I., Mcgowan, M. M., Tsapakos, M. J., Ripple, G. H., Suriawinata, A. A., ... Barth, R. J. (2012). Neoadjuvant cetuximab, twice-weekly gemcitabine, and intensity-modulated radiotherapy (IMRT) in patients with pancreatic adenocarcinoma. Annals of Oncology, 23(11), 2820-2827. [mds109]. https://doi.org/10.1093/annonc/mds109

Neoadjuvant cetuximab, twice-weekly gemcitabine, and intensity-modulated radiotherapy (IMRT) in patients with pancreatic adenocarcinoma. / Pipas, J. M.; Zaki, B. I.; Mcgowan, M. M.; Tsapakos, M. J.; Ripple, G. H.; Suriawinata, A. A.; Tsongalis, G. J.; Colacchio, T. A.; Gordon, S. R.; Sutton, J. E.; Srivastava, A.; Smith, K. D.; Gardner, T. B.; Korc, M.; Davis, T. H.; Preis, M.; Tarczewski, S. M.; Mackenzie, T. A.; Barth, R. J.

In: Annals of Oncology, Vol. 23, No. 11, mds109, 01.11.2012, p. 2820-2827.

Research output: Contribution to journalArticle

Pipas, JM, Zaki, BI, Mcgowan, MM, Tsapakos, MJ, Ripple, GH, Suriawinata, AA, Tsongalis, GJ, Colacchio, TA, Gordon, SR, Sutton, JE, Srivastava, A, Smith, KD, Gardner, TB, Korc, M, Davis, TH, Preis, M, Tarczewski, SM, Mackenzie, TA & Barth, RJ 2012, 'Neoadjuvant cetuximab, twice-weekly gemcitabine, and intensity-modulated radiotherapy (IMRT) in patients with pancreatic adenocarcinoma', Annals of Oncology, vol. 23, no. 11, mds109, pp. 2820-2827. https://doi.org/10.1093/annonc/mds109
Pipas, J. M. ; Zaki, B. I. ; Mcgowan, M. M. ; Tsapakos, M. J. ; Ripple, G. H. ; Suriawinata, A. A. ; Tsongalis, G. J. ; Colacchio, T. A. ; Gordon, S. R. ; Sutton, J. E. ; Srivastava, A. ; Smith, K. D. ; Gardner, T. B. ; Korc, M. ; Davis, T. H. ; Preis, M. ; Tarczewski, S. M. ; Mackenzie, T. A. ; Barth, R. J. / Neoadjuvant cetuximab, twice-weekly gemcitabine, and intensity-modulated radiotherapy (IMRT) in patients with pancreatic adenocarcinoma. In: Annals of Oncology. 2012 ; Vol. 23, No. 11. pp. 2820-2827.
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abstract = "Background: Neoadjuvant therapy has been investigated for localized and locally advanced pancreatic ductal adenocarcinoma (PDAC) but no standard of care exists. Combination cetuximab/gemcitabine/radiotherapy demonstrates encouraging preclinical activity in PDAC. We investigated cetuximab with twice-weekly gemcitabine and intensity-modulated radiotherapy (IMRT) as neoadjuvant therapy in patients with localized or locally advanced PDAC. Experimental design: Treatment consisted of cetuximab load at 400 mg/m.2 followed by cetuximab 250 mg/m.2 weekly and gemcitabine 50 mg/m.2 twice-weekly given concurrently with IMRT to 54 Gy. Following therapy, patients were considered for resection. Results: Thirty-seven patients were enrolled with 33 assessable for response. Ten patients (30{\%}) manifested partial response and 20 (61{\%}) manifested stable disease by RECIST. Twenty-five patients (76{\%}) underwent resection, including 18/23 previously borderline and 3/6 previously unresectable tumors. Twenty-three (92{\%}) of these had negative surgical margins. Pathology revealed that 24{\%} of resected tumors had grade III/IV tumor kill, including two pathological complete responses (8{\%}). Median survival was 24.3 months in resected patients. Outcome did not vary by epidermal growth factor receptor status. Conclusions: Neoadjuvant therapy with cetuximab/gemcitabine/IMRT is tolerable and active in PDAC. Margin-negative resection rates are high and some locally advanced tumors can be downstaged to allow for complete resection with encouraging survival. Pathological complete responses can occur. This combination warrants further investigation.",
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T1 - Neoadjuvant cetuximab, twice-weekly gemcitabine, and intensity-modulated radiotherapy (IMRT) in patients with pancreatic adenocarcinoma

AU - Pipas, J. M.

AU - Zaki, B. I.

AU - Mcgowan, M. M.

AU - Tsapakos, M. J.

AU - Ripple, G. H.

AU - Suriawinata, A. A.

AU - Tsongalis, G. J.

AU - Colacchio, T. A.

AU - Gordon, S. R.

AU - Sutton, J. E.

AU - Srivastava, A.

AU - Smith, K. D.

AU - Gardner, T. B.

AU - Korc, M.

AU - Davis, T. H.

AU - Preis, M.

AU - Tarczewski, S. M.

AU - Mackenzie, T. A.

AU - Barth, R. J.

PY - 2012/11/1

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N2 - Background: Neoadjuvant therapy has been investigated for localized and locally advanced pancreatic ductal adenocarcinoma (PDAC) but no standard of care exists. Combination cetuximab/gemcitabine/radiotherapy demonstrates encouraging preclinical activity in PDAC. We investigated cetuximab with twice-weekly gemcitabine and intensity-modulated radiotherapy (IMRT) as neoadjuvant therapy in patients with localized or locally advanced PDAC. Experimental design: Treatment consisted of cetuximab load at 400 mg/m.2 followed by cetuximab 250 mg/m.2 weekly and gemcitabine 50 mg/m.2 twice-weekly given concurrently with IMRT to 54 Gy. Following therapy, patients were considered for resection. Results: Thirty-seven patients were enrolled with 33 assessable for response. Ten patients (30%) manifested partial response and 20 (61%) manifested stable disease by RECIST. Twenty-five patients (76%) underwent resection, including 18/23 previously borderline and 3/6 previously unresectable tumors. Twenty-three (92%) of these had negative surgical margins. Pathology revealed that 24% of resected tumors had grade III/IV tumor kill, including two pathological complete responses (8%). Median survival was 24.3 months in resected patients. Outcome did not vary by epidermal growth factor receptor status. Conclusions: Neoadjuvant therapy with cetuximab/gemcitabine/IMRT is tolerable and active in PDAC. Margin-negative resection rates are high and some locally advanced tumors can be downstaged to allow for complete resection with encouraging survival. Pathological complete responses can occur. This combination warrants further investigation.

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KW - Cetuximab

KW - Gemcitabine

KW - Intensity-modulated radiotherapy

KW - Neoadjuvant therapy

KW - Pancreatic cancer

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