title: Multicenter phase II trial to investigate safety and efficacy of gemcitabine combined with cetuximab as adjuvant therapy in pancreatic cancer (ATIP).
abstract: BACKGROUND
  To investigate whether addition of cetuximab to standard adjuvant chemotherapy with gemcitabine improves outcome in pancreatic cancer, specifically whether the rate of disease-free survival (DFS) at 18 months (primary end point) exceeds the previously reported 35% of gemcitabine alone.
  
  
  METHODS
  Prospective, open-label, multicenter, nonrandomized phase II study in 76 patients with R0- or R1-resected ductal adenocarcinoma of the pancreas included between October 2006 and November 2008. Gemcitabine and cetuximab were administered for 24 weeks. Secondary end points included overall survival (OS) and toxic effect.
  
  
  RESULTS
  Seventy-three patients received cetuximab. Median DFS was 10.0 [95% confidence interval (CI) 8.9-13.6] months and the DFS rate at month 18 of 27.1% (16.7%-37.6%) was inferior to 35%. Median OS was 22.4 (18.2-27.9) months. Subgroup analyses revealed a nonsignificant increase in DFS for patients with versus without skin toxic effect ≥ grade 2 (median 14.7 versus 8.3 months, P = 0.073) and wild-type versus mutated K-Ras (median 11.5 versus 9.3 months, P = 0.57). Grade 3/4 toxic effects included neutropenia (11.0%), thrombopenia (7%), skin toxic effect (7%) and allergic reactions (7%).
  
  
  CONCLUSIONS
  Addition of cetuximab to adjuvant gemcitabine does not seem to improve DFS or OS of unstratified pancreatic cancer patients. Trends for improved DFS in patients with wild-type K-Ras and skin toxic effect remain to be confirmed.
authors.affiliation: Department of Gastroenterology.
authors.forename: H
authors.initials: H
authors.lastname: Fensterer
authors.affiliation: Coordinating Centre for Clinical Trials.
authors.forename: C
authors.initials: C
authors.lastname: Schade-Brittinger
authors.affiliation: Department of Institute for Medical Informatics, Biometry and Epidemiology, University of Munich, Munich.
authors.forename: H-H
authors.initials: HH
authors.lastname: Müller
authors.affiliation: Department of Oncology.
authors.forename: S
authors.initials: S
authors.lastname: Tebbe
authors.affiliation: Department of Surgery, Clinical Centre Kassel, Kassel.
authors.forename: J
authors.initials: J
authors.lastname: Fass
authors.affiliation: Department of Hematology.
authors.forename: U
authors.initials: U
authors.lastname: Lindig
authors.affiliation: Department of Surgery, University of Jena, Jena.
authors.forename: U
authors.initials: U
authors.lastname: Settmacher
authors.affiliation: Medical Department I, Ruhr-University Bochum, Bochum.
authors.forename: W E
authors.initials: WE
authors.lastname: Schmidt
authors.affiliation: Department of Surgery, National Centre for Tumour Disease, University of Heidelberg, Heidelberg.
authors.forename: A
authors.initials: A
authors.lastname: Märten
authors.affiliation: Medical Department II.
authors.forename: M P
authors.initials: MP
authors.lastname: Ebert
authors.affiliation: Department of Surgery, University of Ulm, Ulm.
authors.forename: M
authors.initials: M
authors.lastname: Kornmann
authors.affiliation: Day Treatment Centre at the Interdisciplinary Tumour Centre, University Hospital Mannheim, Mannheim.
authors.forename: R
authors.initials: R
authors.lastname: Hofheinz
authors.affiliation: Department of Gastroenterology, University Clinic Regensburg, Regensburg.
authors.forename: E
authors.initials: E
authors.lastname: Endlicher
authors.affiliation: Department of Hematology, Philipps-University of Marburg, Marburg.
authors.forename: C
authors.initials: C
authors.lastname: Brendel
authors.affiliation: Institute of Pathology, University of Marburg, University Hospital Münster, Germany.
authors.forename: P J
authors.initials: PJ
authors.lastname: Barth
authors.affiliation: Department of Surgery.
authors.forename: D K
authors.initials: DK
authors.lastname: Bartsch
authors.affiliation: Department of Gastroenterology.
authors.forename: P
authors.initials: P
authors.lastname: Michl
authors.affiliation: Department of Gastroenterology. Electronic address: gress@med.uni-marburg.de.
authors.forename: T M
authors.initials: TM
authors.lastname: Gress
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; 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*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D000068818:Cetuximab; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics; D000093542:Gemcitabine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D003841:Deoxycytidine; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D000093542:Gemcitabine
keywords: adjuvant chemotherapy; cetuximab; gemcitabine; pancreatic cancer