title: Neoadjuvant cetuximab, twice-weekly gemcitabine, and intensity-modulated radiotherapy (IMRT) in patients with pancreatic adenocarcinoma.
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.
  
  
  METHODS
  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.
authors.affiliation: Section Hematology/Oncology, Department of Medicine. Electronic address: J.Marc.Pipas@Hitchcock.org.
authors.forename: J M
authors.initials: JM
authors.lastname: Pipas
authors.affiliation: Section Radiation Oncology, Department of Medicine.
authors.forename: B I
authors.initials: BI
authors.lastname: Zaki
authors.affiliation: Section Hematology/Oncology, Department of Medicine.
authors.forename: M M
authors.initials: MM
authors.lastname: McGowan
authors.affiliation: Department of Radiology.
authors.forename: M J
authors.initials: MJ
authors.lastname: Tsapakos
authors.affiliation: Section Hematology/Oncology, Department of Medicine.
authors.forename: G H
authors.initials: GH
authors.lastname: Ripple
authors.affiliation: Department of Pathology.
authors.forename: A A
authors.initials: AA
authors.lastname: Suriawinata
authors.affiliation: Department of Pathology.
authors.forename: G J
authors.initials: GJ
authors.lastname: Tsongalis
authors.affiliation: Section Surgical Oncology, Department of Surgery.
authors.forename: T A
authors.initials: TA
authors.lastname: Colacchio
authors.affiliation: Section Gastroenterology, Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon.
authors.forename: S R
authors.initials: SR
authors.lastname: Gordon
authors.affiliation: Department of Surgery, Veterans Administration Medical Center, White River Junction.
authors.forename: J E
authors.initials: JE
authors.lastname: Sutton
authors.affiliation: Department of Pathology, Brigham & Women's Hospital, Boston.
authors.forename: A
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Section Surgical Oncology, Department of Surgery.
authors.forename: K D
authors.initials: KD
authors.lastname: Smith
authors.affiliation: Section Gastroenterology, Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon.
authors.forename: T B
authors.initials: TB
authors.lastname: Gardner
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis.
authors.forename: M
authors.initials: M
authors.lastname: Korc
authors.affiliation: Section Hematology/Oncology, Department of Medicine.
authors.forename: T H
authors.initials: TH
authors.lastname: Davis
authors.affiliation: Section Hematology/Oncology, Department of Medicine.
authors.forename: M
authors.initials: M
authors.lastname: Preis
authors.affiliation: Office of Clinical Research, Norris Cotton Cancer Center, Lebanon.
authors.forename: S M
authors.initials: SM
authors.lastname: Tarczewski
authors.affiliation: Department of Epidemiology & Biostatistics, Dartmouth-Hitchcock Medical Center, Lebanon, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: MacKenzie
authors.affiliation: Section Surgical Oncology, Department of Surgery.
authors.forename: R J
authors.initials: RJ
authors.lastname: Barth
mesh_terms: D000230:Adenocarcinoma / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068818:Cetuximab; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D010190:Pancreatic Neoplasms / Q000628:therapy*; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D003841:Deoxycytidine; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab; D000093542:Gemcitabine