title: A randomised phase II trial and feasibility study of palliative chemotherapy in frail or elderly patients with advanced gastroesophageal cancer (321GO).
abstract: BACKGROUND
  Elderly patients are commonly under-represented in cancer clinical trials. The 321GO was undertaken in preparation for a definitive phase three trial assessing different chemotherapy regimens in a frail and/or elderly population with advanced gastroesophageal (GO) cancer.
  
  
  METHODS
  Patients with advanced GO cancer considered unfit for conventional dose chemotherapy were randomly assigned in a 1 : 1 : 1 ratio to: epirubicin, oxaliplatin and capecitabine (EOX); oxaliplatin and capecitabine (OX); and capecitabine alone (X) (all 80% of full dose and unblinded). The primary end point was patient recruitment over an 18-month period. A registration study recorded treatment choice for all patients with advanced GO cancer at trial centres.
  
  
  RESULTS
  A total of 313 patients were considered for palliative chemotherapy for GO cancer over the 18-month period: 115 received full dose treatment, 89 less than standard treatment or entered 321GO and 111 no treatment. Within 321GO, 55 patients were randomly assigned (19 to OX and X; 17 to EOX). Progression-free survival (PFS) for all patients was 4.4 months and by arm 5.4, 5.6 and 3.0 months for EOX, OX and X, respectively. The number of patients with a good overall treatment utility (OTU), a novel patient-centred endpoint, at 12 weeks was 3 (18%), 6 (32%) and 1 (6%) for EOX, OX and X, respectively. At 6 weeks, 22 patients (41%) had experienced a non-haematologic toxicity ⩾grade 3, most commonly lethargy or diarrhoea. The OTU was prognostic for overall survival in patients alive at week 12 (logrank test P=0.0001).
  
  
  CONCLUSIONS
  It is feasible to recruit elderly and/or frail patients with advanced GO cancer to a randomised clinical trial. The OX is the preferred regimen for further study. Overall treatment utility shows promise as a comparator between treatment regimens for feasibility and randomised trials in the elderly and/or frail GO cancer population.
authors.affiliation: Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh EH4 2XR, UK.
authors.forename: P S
authors.initials: PS
authors.lastname: Hall
authors.affiliation: Department of Oncology, University of Oxford, Oxford, UK.
authors.forename: S R
authors.initials: SR
authors.lastname: Lord
authors.affiliation: Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: M
authors.initials: M
authors.lastname: Collinson
authors.affiliation: Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: H
authors.initials: H
authors.lastname: Marshall
authors.affiliation: Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: M
authors.initials: M
authors.lastname: Jones
authors.affiliation: NIHR Cancer Research Network Coordinating Centre, Leeds, UK.
authors.forename: C
authors.initials: C
authors.lastname: Lowe
authors.affiliation: Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: H
authors.initials: H
authors.lastname: Howard
authors.affiliation: Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
authors.forename: D
authors.initials: D
authors.lastname: Swinson
authors.affiliation: Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
authors.forename: G
authors.initials: G
authors.lastname: Velikova
authors.affiliation: Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
authors.forename: A
authors.initials: A
authors.lastname: Anthoney
authors.affiliation: Department of Oncology, Castle Hill Hospital, Hull, UK.
authors.forename: R
authors.initials: R
authors.lastname: Roy
authors.affiliation: Department of Oncology, Huddersfield Royal Infirmary, Huddersfield, UK.
authors.forename: J
authors.initials: J
authors.lastname: Dent
authors.affiliation: Department of Oncology, The York Hospital, York, UK.
authors.forename: S
authors.initials: S
authors.lastname: Cheeseman
authors.affiliation: Department of Oncology, The York Hospital, York, UK.|Department of Oncology, Bradford Royal Infirmary, Bradford, UK.
authors.forename: K
authors.initials: K
authors.lastname: Last
authors.affiliation: NIHR Cancer Research Network Coordinating Centre, Leeds, UK.
authors.forename: M T
authors.initials: MT
authors.lastname: Seymour
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D016330:Frail Elderly; D006801:Humans; D008297:Male; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010166:Palliative Care / Q000379:methods*
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D015251:Epirubicin; D000069287:Capecitabine; D005472:Fluorouracil