title: Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial.
abstract: BACKGROUND
  Second-line chemotherapy for patients with oesophagogastric adenocarcinoma refractory to platinum and fluoropyrimidines has not shown benefits in health-related quality of life (HRQoL). We assessed whether the addition of docetaxel to active symptom control alone can improve survival and HRQoL for patients.
  
  
  METHODS
  For this open-labelled, multicentre trial, we recruited patients aged 18 years or older from 30 UK centres. Patients were eligible if they had an advanced, histologically confirmed adenocarcinoma of the oesophagus, oesophagogastric junction, or stomach that had progressed on or within 6 months of treatment with a platinum-fluoropyrimidine combination. Patients could have an Eastern Cooperative Oncology Group performance status of 0-2. We randomly assigned patients using a central, computerised minimisation procedure to receive docetaxel plus active symptom control, or active symptom control alone (1:1; stratified by disease status, disease site, duration of response to previous chemotherapy, and performance status). Docetaxel was given at a dose of 75 mg/m(2) by intravenous infusion every 3 weeks for up to six cycles. The primary endpoint was overall survival, analysed by intention to treat. This is the report of the planned final analysis. This study is an International Standardised Randomised Controlled Trial, number ISRCTN13366390.
  
  
  RESULTS
  Between April 21, 2008, and April 26, 2012, we recruited 168 patients, allocating 84 to each treatment group. After a median follow-up of 12 months [IQR 10-21]) and 161 (96%) deaths (80 in the docetaxel group, 81 in the active symptom control group), median overall survival in the docetaxel group was 5.2 months (95% CI 4.1-5.9) versus 3.6 months (3.3-4.4) in the active symptom control group (hazard ratio 0.67, 95% CI 0.49-0.92; p=0.01). Docetaxel was associated with higher incidence of grade 3-4 neutropenia (12 [15%] patients vs no patients), infection (15 [19%] patients vs two [3%] patients), and febrile neutropenia (six [7%] patients vs no patients). Patients receiving docetaxel reported less pain (p=0.0008) and less nausea and vomiting (p=0.02) and constipation (p=0.02). Global HRQoL was similar between the groups (p=0.53). Disease specific HRQoL measures also showed benefits for docetaxel in reducing dysphagia (p=0.02) and abdominal pain (p=0.01).
  
  
  CONCLUSIONS
  Our findings suggest that docetaxel can be recommended as an appropriate second-line treatment for patients with oesophagogastric adenocarcinoma that is refractory to treatment with platinum and fluoropyrimidine.
  
  
  BACKGROUND
  Cancer Research UK.
authors: Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. Electronic address: hugo.ford@addenbrookes.nhs.uk.
authors: Hugo E R
authors: HE
authors: Ford
authors: Warwick Clinical Trials Unit, Coventry, UK.
authors: Andrea
authors: A
authors: Marshall
authors: University College London Cancer Institute, Huntley Street, London, UK.
authors: John A
authors: JA
authors: Bridgewater
authors: Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
authors: Tobias
authors: T
authors: Janowitz
authors: Newcastle General Hospital, Newcastle, UK.
authors: Fareeda Y
authors: FY
authors: Coxon
authors: Weston Park Hospital, Sheffield, UK.
authors: Jonathan
authors: J
authors: Wadsley
authors: Christie Hospital, Manchester, UK.
authors: Wasat
authors: W
authors: Mansoor
authors: Lancaster Royal Infirmary, Lancaster, UK.
authors: David
authors: D
authors: Fyfe
authors: Queens Medical Centre, Nottingham, UK.
authors: Srinivasan
authors: S
authors: Madhusudan
authors: Royal Surrey County Hospital, Guildford, UK.
authors: Gary W
authors: GW
authors: Middleton
authors: St James' University Hospital, Leeds, UK.
authors: Daniel
authors: D
authors: Swinson
authors: Bristol Haematology and Oncology Centre, Bristol, UK.
authors: Stephen
authors: S
authors: Falk
authors: Royal Marsden Hospital, Sutton, UK.
authors: Ian
authors: I
authors: Chau
authors: Royal Marsden Hospital, Sutton, UK.
authors: David
authors: D
authors: Cunningham
authors: Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
authors: Paula
authors: P
authors: Kareclas
authors: Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
authors: Natalie
authors: N
authors: Cook
authors: University of Bristol, Bristol, UK.
authors: Jane M
authors: JM
authors: Blazeby
authors: Warwick Clinical Trials Unit, Coventry, UK.
authors: Janet A
authors: JA
authors: Dunn
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077143:Docetaxel; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D004943:Esophagogastric Junction; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology; D043823:Taxoids / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel