title: Phase I Clinical Trial to Determine the Feasibility and Maximum Tolerated Dose of Panitumumab to Standard Gemcitabine-Based Chemoradiation in Locally Advanced Pancreatic Cancer.
abstract: OBJECTIVE
  Epidermal growth factor receptor (EGFR) inhibitors may improve both the therapeutic efficacy of radiotherapy and the radiosensitizing activity of gemcitabine. Based on this rationale and the nonoverlapping toxicity profiles of gemcitabine and the monoclonal EGFR antibody panitumumab, we designed a phase I trial to investigate the maximum-tolerated dose (MTD), safety, and activity of panitumumab added to gemcitabine-based chemoradiotherapy (CRT) in patients with locally advanced pancreatic cancer (LAPC).
  
  
  METHODS
  Patients with LAPC and WHO performance status 0 to 1 were treated with weekly panitumumab at four dose levels (1-2.5 mg/kg), combined with weekly gemcitabine 300 mg/m(2) and radiotherapy (50.4 Gy in 28 fractions) for 6 weeks, followed by gemcitabine 1,000 mg/m(2) weekly for 3 weeks every 4 weeks until disease progression or unacceptable toxicity. Each cohort was monitored during the combination therapy to establish dose limiting toxicity. Tumor evaluation was performed after CRT and during gemcitabine monotherapy.
  
  
  RESULTS
  Fourteen patients were enrolled; 14 were evaluable for toxicity and 13 for response. The MTD for panitumumab was 1.5 mg/kg. Three of the 6 patients, treated at MTD, experienced grade 3 adverse events during the combination therapy; neutropenia (n = 2; 33%), fatigue (n = 1; 17%), nausea (n = 1; 17%), and vomiting (n = 1; 17%). Partial response was achieved by 3 patients (23%), 1 in each dose cohort. Median progression free survival of the three cohorts together was 8.9 months.
  
  
  CONCLUSIONS
  The addition of panitumumab to gemcitabine-based chemoradiotherapy in LAPC has manageable toxicity and potential clinical efficacy.
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Annette A
authors.initials: AA
authors.lastname: van Zweeden
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: van der Vliet
authors.affiliation: Department of Medical Oncology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Johanna W
authors.initials: JW
authors.lastname: Wilmink
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Martijn R
authors.initials: MR
authors.lastname: Meijerink
authors.affiliation: Department of Radiation Oncology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Otto W M
authors.initials: OW
authors.lastname: Meijer
authors.affiliation: Department of Radiation Oncology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Anna M E
authors.initials: AM
authors.lastname: Bruynzeel
authors.affiliation: Department of Radiation Oncology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Geertjan
authors.initials: G
authors.lastname: van Tienhoven
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Elisa
authors.initials: E
authors.lastname: Giovannetti
authors.affiliation: Department of Surgery, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: Kazemier
authors.affiliation: Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Maarten A J M
authors.initials: MA
authors.lastname: Jacobs
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands. h.verheul@vumc.nl.
authors.forename: Henk M W
authors.initials: HM
authors.lastname: Verheul
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D059248:Chemoradiotherapy / Q000379:methods; D003131:Combined Modality Therapy / Q000379:methods; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D000077544:Panitumumab; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000077544:Panitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D000093542:Gemcitabine