title: Docetaxel plus oxaliplatin with or without fluorouracil or capecitabine in metastatic or locally recurrent gastric cancer: a randomized phase II study.
abstract: BACKGROUND
  Docetaxel/cisplatin/infusional 5-fluorouracil (5-FU; DCF) is a standard chemotherapy regimen for patients with advanced gastric cancer (GC). This phase II study evaluated docetaxel/oxaliplatin (TE), docetaxel/oxaliplatin/5-FU (TEF), and docetaxel/oxaliplatin/capecitabine (TEX) in patients with advanced GC.
  
  
  METHODS
  Patients with metastatic or locally recurrent gastric adenocarcinoma (including carcinoma of the gastro-oesophageal junction) were randomly assigned (1 : 1 : 1) to TE, TEF, or TEX. Each regimen was tested at two doses before full evaluation at optimized dose levels. The primary end point was progression-free survival (PFS). Overall survival (OS), tumour response, and safety were also assessed. A therapeutic index (median PFS relative to the incidence of febrile neutropenia) was calculated for each regimen and compared with DCF (historical data).
  
  
  RESULTS
  Overall, 248 patients were randomly assigned to receive optimized dose treatment. Median PFS was longer with TEF (7.66 [95% confidence interval (CI): 6.97-9.40] months) versus TE (4.50 [3.68-5.32] months) and TEX (5.55 [4.30-6.37] months). Median OS was 14.59 (95% CI: 11.70-21.78) months for TEF versus 8.97 (7.79-10.87) months for TE and 11.30 (8.08-14.03) months for TEX. The rate of tumour response (complete or partial) was 46.6% (95% CI 35.9-57.5) for TEF versus 23.1% (14.3-34.0) for TE and 25.6% (16.6-36.4) for TEX. The frequency and type of adverse events (AEs) were similar across the three arms. Common grade 3/4 AEs were fatigue (21%), sensory neuropathy (14%), and diarrhoea (13%). Febrile neutropenia was reported in 2% (TEF), 14% (TE), and 9% (TEX) of patients. The therapeutic index was improved with TEF versus TEX, TE, or DCF.
  
  
  CONCLUSIONS
  These results suggest that TEF is worthy of evaluation as an arm in a phase III trial or as a backbone regimen for new targeted agents in advanced GC. CLINICALTRIALS.GOV: Identifier Trial registration number: NCT00382720.
authors.affiliation: Digestive Oncology, University Hospitals Leuven and KU Leuven, Leuven, Belgium. Electronic address: eric.vancutsem@uzleuven.be.
authors.forename: E
authors.initials: E
authors.lastname: Van Cutsem
authors.affiliation: Department of Oncology, Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Boni
authors.affiliation: Department of Medical Oncology, Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona.
authors.forename: J
authors.initials: J
authors.lastname: Tabernero
authors.affiliation: Medical Oncology Service, Alicante University Hospital, Alicante, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Massuti
authors.affiliation: Department of Medical Oncology, University of Birmingham, Birmingham, UK.
authors.forename: G
authors.initials: G
authors.lastname: Middleton
authors.affiliation: Department of Medical Oncology, Marmara University Medical Faculty, Istanbul, Turkey.
authors.forename: F
authors.initials: F
authors.lastname: Dane
authors.affiliation: Interdisciplinary Oncology, HELIOS Klinikum Berlin-Buch, Berlin, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Reichardt
authors.affiliation: Oncology, Hospital de São Sebastião, Santa Maria da Feira, Portugal.
authors.forename: F L
authors.initials: FL
authors.lastname: Pimentel
authors.affiliation: US Oncology Research, Rocky Mountain Cancer Centers, Denver, USA.
authors.forename: A
authors.initials: A
authors.lastname: Cohn
authors.affiliation: Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France.
authors.forename: P
authors.initials: P
authors.lastname: Follana
authors.affiliation: Department of Internal Medicine I, Klinikum Mutterhaus der Borromaeerinnen, Trier, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Clemens
authors.affiliation: Medical Oncology, Fondazione Poliambulanza - Istituto Ospedaliero, Brescia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Zaniboni
authors.affiliation: Medical Oncology, N.N. Petrov Oncology SRI, St Petersburg, Russia.
authors.forename: V
authors.initials: V
authors.lastname: Moiseyenko
authors.affiliation: Department of Clinical Oncology, Mount Vernon Cancer Centre, Northwood, UK.
authors.forename: M
authors.initials: M
authors.lastname: Harrison
authors.affiliation: US Oncology Research, Texas Oncology-Tyler, Tyler, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Richards
authors.affiliation: Digestive Oncology, University Hospitals Leuven and KU Leuven, Leuven, Belgium.
authors.forename: H
authors.initials: H
authors.lastname: Prenen
authors.affiliation: Digestive Oncology, Universite Paris-V European Hospital Georges Pompidou, APHP, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Pernot
authors.affiliation: Medical Operations, Sanofi K.K., Tokyo, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Ecstein-Fraisse
authors.affiliation: Statistics, Sanofi, Chilly-Mazarin, France.
authors.forename: S
authors.initials: S
authors.lastname: Hitier
authors.affiliation: Digestive Oncology, Universite Paris-V European Hospital Georges Pompidou, APHP, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Rougier
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D000069287:Capecitabine; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000077150:Oxaliplatin; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D043823:Taxoids; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000077143:Docetaxel; D000069287:Capecitabine; D005472:Fluorouracil