title: A phase II study of epirubicin, cisplatin and raltitrexed combination chemotherapy (ECT) in patients with advanced oesophageal and gastric adenocarcinoma.
abstract: BACKGROUND
  The aim of this study was to evaluate the efficacy of the combination of epirubicin, cisplatin and ralitrexed (Tomudex). ECT, in patients with advanced oesophageal or gastric adenocarcinoma. Efficacy was assessed primarily as response rate and secondarily in terms of toxicity, time to progression and survival.
  
  
  METHODS
  Twenty-one patients with histologically and/or cytologically proven unresectable (7) or metastatic (14) gastro-oesophageal adenocarcinoma, who had bi-dimensionally measurable disease, with ECOG performance status < or = 2. with adequate haematological, hepatic and renal function received first-line chemotherapy with epirubicin (50 mg/m2). cisplatin (60 mg/m2) and Tomudex (2.5 mg/m2), ECT, at three-weekly intervals. Treatment consisted of three cycles of chemotherapy, with a further three cycles if there was disease response or stabilisation.
  
  
  RESULTS
  ECT is an active regimen in the treatment of advanced gastro-oesophageal adenocarcinoma with an overall intention-to-treat response rate of 29% (95% confidence intervals (CI): 11%-52%). In addition, 4 (19%) patients had stable disease. Median time to progression was 19 weeks (95% CI: 7-31 weeks). Median overall survival was 18 weeks (95% CI: 11-24 weeks). Seventeen patients failed to complete the six cycles of treatment due to disease progression (5). toxicity (3), non-toxic death (1 pulmonary embolism, 1 cardiac), severe allergy to epirubicin (1), patient decision (1) and five patients after the study was discontinued early due to toxicity. There were three toxic deaths: two due to sepsis complicating neutropaenia and one due to cardiorespiratory failure following drug induced enteritis. Nine patients experienced grade 3 or 4 neutropaenia, two patients experienced grade 3 or 4 nausea and vomiting and one patient had grade 4 diarrhoea.
  
  
  CONCLUSIONS
  The combination of epirubicin, cisplatin and tomudex is active against advanced gastro-oesophageal adenocarcinoma but the toxicity suggests that further evaluation in a randomised comparison to ECF is not appropriate.
authors.affiliation: CRC Department of Medical Oncology Beatson Oncology Centre, Western Infirmary, Glasgow, UK. hjmklz@udcf.gla.ac.uk
authors.forename: H J
authors.initials: HJ
authors.lastname: Mackay
authors.forename: A
authors.initials: A
authors.lastname: McInnes
authors.forename: J
authors.initials: J
authors.lastname: Paul
authors.forename: N
authors.initials: N
authors.lastname: Raby
authors.forename: F J
authors.initials: FJ
authors.lastname: Lofts
authors.forename: A C
authors.initials: AC
authors.lastname: McDonald
authors.forename: M
authors.initials: M
authors.lastname: Soukop
authors.forename: G M
authors.initials: GM
authors.lastname: Fullarton
authors.forename: A L
authors.initials: AL
authors.lastname: Harris
authors.forename: J
authors.initials: J
authors.lastname: Garcia-Vargas
authors.forename: T R
authors.initials: TR
authors.lastname: Evans
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D004342:Drug Hypersensitivity; D004751:Enteritis / Q000139:chemically induced; D015251:Epirubicin / Q000008:administration & dosage; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D011655:Pulmonary Embolism / Q000139:chemically induced; D011799:Quinazolines / Q000008:administration & dosage; D018805:Sepsis / Q000139:chemically induced / Q000401:mortality; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D013876:Thiophenes / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D011799:Quinazolines; D013876:Thiophenes; D015251:Epirubicin; D002945:Cisplatin