PMID- 25416687 OWN - NLM STAT- MEDLINE DCOM- 20150824 LR - 20240229 IS - 1569-8041 (Electronic) IS - 0923-7534 (Linking) VI - 26 IP - 1 DP - 2015 Jan TI - Docetaxel plus oxaliplatin with or without fluorouracil or capecitabine in metastatic or locally recurrent gastric cancer: a randomized phase II study. PG - 149-156 LID - S0923-7534(19)31336-5 [pii] LID - 10.1093/annonc/mdu496 [doi] AB - 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. PATIENTS AND 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. CONCLUSION: 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. FAU - Van Cutsem, E AU - Van Cutsem E AD - Digestive Oncology, University Hospitals Leuven and KU Leuven, Leuven, Belgium. Electronic address: eric.vancutsem@uzleuven.be. FAU - Boni, C AU - Boni C AD - Department of Oncology, Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy. FAU - Tabernero, J AU - Tabernero J AD - Department of Medical Oncology, Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autonoma de Barcelona, Barcelona. FAU - Massuti, B AU - Massuti B AD - Medical Oncology Service, Alicante University Hospital, Alicante, Spain. FAU - Middleton, G AU - Middleton G AD - Department of Medical Oncology, University of Birmingham, Birmingham, UK. FAU - Dane, F AU - Dane F AD - Department of Medical Oncology, Marmara University Medical Faculty, Istanbul, Turkey. FAU - Reichardt, P AU - Reichardt P AD - Interdisciplinary Oncology, HELIOS Klinikum Berlin-Buch, Berlin, Germany. FAU - Pimentel, F L AU - Pimentel FL AD - Oncology, Hospital de Sao Sebastiao, Santa Maria da Feira, Portugal. FAU - Cohn, A AU - Cohn A AD - US Oncology Research, Rocky Mountain Cancer Centers, Denver, USA. FAU - Follana, P AU - Follana P AD - Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France. FAU - Clemens, M AU - Clemens M AD - Department of Internal Medicine I, Klinikum Mutterhaus der Borromaeerinnen, Trier, Germany. FAU - Zaniboni, A AU - Zaniboni A AD - Medical Oncology, Fondazione Poliambulanza - Istituto Ospedaliero, Brescia, Italy. FAU - Moiseyenko, V AU - Moiseyenko V AD - Medical Oncology, N.N. Petrov Oncology SRI, St Petersburg, Russia. FAU - Harrison, M AU - Harrison M AD - Department of Clinical Oncology, Mount Vernon Cancer Centre, Northwood, UK. FAU - Richards, D A AU - Richards DA AD - US Oncology Research, Texas Oncology-Tyler, Tyler, USA. FAU - Prenen, H AU - Prenen H AD - Digestive Oncology, University Hospitals Leuven and KU Leuven, Leuven, Belgium. FAU - Pernot, S AU - Pernot S AD - Digestive Oncology, Universite Paris-V European Hospital Georges Pompidou, APHP, Paris, France. FAU - Ecstein-Fraisse, E AU - Ecstein-Fraisse E AD - Medical Operations, Sanofi K.K., Tokyo, Japan. FAU - Hitier, S AU - Hitier S AD - Statistics, Sanofi, Chilly-Mazarin, France. FAU - Rougier, P AU - Rougier P AD - Digestive Oncology, Universite Paris-V European Hospital Georges Pompidou, APHP, Paris, France. LA - eng SI - ClinicalTrials.gov/NCT00382720 PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - England TA - Ann Oncol JT - Annals of oncology : official journal of the European Society for Medical Oncology JID - 9007735 RN - 0 (Antineoplastic Agents) RN - 0 (Organoplatinum Compounds) RN - 0 (Taxoids) RN - 04ZR38536J (Oxaliplatin) RN - 0W860991D6 (Deoxycytidine) RN - 15H5577CQD (Docetaxel) RN - 6804DJ8Z9U (Capecitabine) RN - U3P01618RT (Fluorouracil) SB - IM MH - Adenocarcinoma/drug therapy/mortality MH - Antineoplastic Agents/adverse effects/therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use MH - Capecitabine MH - Deoxycytidine/adverse effects/*analogs & derivatives/therapeutic use MH - Disease-Free Survival MH - Docetaxel MH - Drug Administration Schedule MH - Female MH - Fluorouracil/adverse effects/*analogs & derivatives/*therapeutic use MH - Humans MH - Male MH - Middle Aged MH - Neoplasm Recurrence, Local/drug therapy/mortality MH - Organoplatinum Compounds/adverse effects/*therapeutic use MH - Oxaliplatin MH - Prospective Studies MH - Stomach Neoplasms/*drug therapy/mortality MH - Taxoids/adverse effects/*therapeutic use MH - Treatment Outcome EDAT- 2014/11/25 06:00 MHDA- 2015/08/25 06:00 CRDT- 2014/11/23 06:00 PHST- 2014/11/23 06:00 [entrez] PHST- 2014/11/25 06:00 [pubmed] PHST- 2015/08/25 06:00 [medline] AID - S0923-7534(19)31336-5 [pii] AID - 10.1093/annonc/mdu496 [doi] PST - ppublish SO - Ann Oncol. 2015 Jan;26(1):149-156. doi: 10.1093/annonc/mdu496.