title: Patterns of progression, treatment of progressive disease and post-progression survival in the New EPOC study.
abstract: BACKGROUND
  The addition of cetuximab (CTX) to perioperative chemotherapy (CT) for operable colorectal liver metastases resulted in a shorter progression-free survival. Details of disease progression are described to further inform the primary study outcome.
  
  
  METHODS
  A total of 257 KRAS wild-type patients were randomised to CT alone or CT with CTX. Data regarding sites and treatment of progressive disease were obtained for the 109 (CT n=48, CT and CTX n=61) patients with progressive disease at the cut-off date for analysis of November 2012.
  
  
  RESULTS
  The liver was the most frequent site of progression (CT 67% (32/48); CT and CTX 66% (40/61)). A higher proportion of patients in the CT and group had multiple sites of progressive disease (CT 8%, 4/48; CT and CTX 23%, 14/61 P=0.04). Further treatment for progressive disease is known for 84 patients of whom 69 received further CT, most frequently irinotecan based. Twenty-two patients, 11 in each arm, received CTX as a further line agent.
  
  
  CONCLUSIONS
  Both the distribution of progressive disease and further treatment are as expected for such a cohort. The pattern of disease progression seen is consistent with failure of systemic micrometastatic disease control rather than failure of local disease control following liver surgery.
authors.affiliation: University Surgery and Cancer Sciences Division, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors.forename: Siân A
authors.initials: SA
authors.lastname: Pugh
authors.affiliation: Southampton Clinical Trials Unit, Southampton, UK.
authors.forename: Megan
authors.initials: M
authors.lastname: Bowers
authors.affiliation: Royal Bournemouth Hospital, Bournemouth, UK.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Ball
authors.affiliation: Bristol Cancer Institute, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Falk
authors.affiliation: Bristol Cancer Institute, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.|Department of Upper Gastrointestinal Surgery, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
authors.forename: Meg
authors.initials: M
authors.lastname: Finch-Jones
authors.affiliation: University of Manchester/The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Juan W
authors.initials: JW
authors.lastname: Valle
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Central Manchester NHS Foundation Trust, Manchester, UK.|Institute of Cancer Sciences, University of Manchester, Manchester, UK.
authors.forename: Derek A
authors.initials: DA
authors.lastname: O'Reilly
authors.affiliation: Hepatobiliary Unit, Manchester Royal Infirmary, Manchester, UK.
authors.forename: Ajith K
authors.initials: AK
authors.lastname: Siriwardena
authors.affiliation: Specialised Cancer Services, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: Hornbuckle
authors.affiliation: Hepatobiliary Surgery, Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK.
authors.forename: Myrddin
authors.initials: M
authors.lastname: Rees
authors.affiliation: Department of Medical Oncology, Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Rees
authors.affiliation: University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Iveson
authors.affiliation: Bournemouth University, Bournemouth, UK.|Poole Hospital, Poole, UK.
authors.forename: Tamas
authors.initials: T
authors.lastname: Hickish
authors.affiliation: Southampton Clinical Trials Unit, Southampton, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Maishman
authors.affiliation: Southampton Clinical Trials Unit, Southampton, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Stanton
authors.affiliation: Southampton Clinical Trials Unit, Southampton, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Dixon
authors.affiliation: Southampton Clinical Trials Unit, Southampton, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Corkhill
authors.affiliation: Southampton Clinical Trials Unit, Southampton, UK.
authors.forename: Mike
authors.initials: M
authors.lastname: Radford
authors.affiliation: Department of Clinical Surgery, The University of Edinburgh, Edinburgh, UK.
authors.forename: O James
authors.initials: OJ
authors.lastname: Garden
authors.affiliation: Department of Medicine, Gastrointestinal and Lymphoma Units, The Royal Marsden Hospital NHS Foundation Trust, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Cunningham
authors.affiliation: Department of Oncology, University of Oxford, Oxford, UK.
authors.forename: Tim S
authors.initials: TS
authors.lastname: Maughan
authors.affiliation: University College London Cancer Institute, London, UK.
authors.forename: John A
authors.initials: JA
authors.lastname: Bridgewater
authors.affiliation: University Surgery and Cancer Sciences Division, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors.forename: John N
authors.initials: JN
authors.lastname: Primrose
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine / Q000008:administration & dosage; D000068818:Cetuximab / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000473:pathology*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006498:Hepatectomy; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D059146:Metastasectomy; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000069287:Capecitabine; D000077146:Irinotecan; D000068818:Cetuximab; D002955:Leucovorin; D002166:Camptothecin