E Van Cutsem1, C Boni2, J Tabernero3, B Massuti4, G Middleton5, F Dane6, P Reichardt7, F L Pimentel8, A Cohn9, P Follana10, M Clemens11, A Zaniboni12, V Moiseyenko13, M Harrison14, D A Richards15, H Prenen16, S Pernot17, E Ecstein-Fraisse18, S Hitier19, P Rougier17. 1. Digestive Oncology, University Hospitals Leuven and KU Leuven, Leuven, Belgium. Electronic address: eric.vancutsem@uzleuven.be. 2. Department of Oncology, Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy. 3. Department of Medical Oncology, Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona. 4. Medical Oncology Service, Alicante University Hospital, Alicante, Spain. 5. Department of Medical Oncology, University of Birmingham, Birmingham, UK. 6. Department of Medical Oncology, Marmara University Medical Faculty, Istanbul, Turkey. 7. Interdisciplinary Oncology, HELIOS Klinikum Berlin-Buch, Berlin, Germany. 8. Oncology, Hospital de São Sebastião, Santa Maria da Feira, Portugal. 9. US Oncology Research, Rocky Mountain Cancer Centers, Denver, USA. 10. Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France. 11. Department of Internal Medicine I, Klinikum Mutterhaus der Borromaeerinnen, Trier, Germany. 12. Medical Oncology, Fondazione Poliambulanza - Istituto Ospedaliero, Brescia, Italy. 13. Medical Oncology, N.N. Petrov Oncology SRI, St Petersburg, Russia. 14. Department of Clinical Oncology, Mount Vernon Cancer Centre, Northwood, UK. 15. US Oncology Research, Texas Oncology-Tyler, Tyler, USA. 16. Digestive Oncology, University Hospitals Leuven and KU Leuven, Leuven, Belgium. 17. Digestive Oncology, Universite Paris-V European Hospital Georges Pompidou, APHP, Paris, France. 18. Medical Operations, Sanofi K.K., Tokyo, Japan. 19. Statistics, Sanofi, Chilly-Mazarin, France.
Abstract
BACKGROUND:Docetaxel/cisplatin/infusional5-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.
RCT Entities:
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.
Authors: Vincent T Janmaat; Ewout W Steyerberg; Ate van der Gaast; Ron Hj Mathijssen; Marco J Bruno; Maikel P Peppelenbosch; Ernst J Kuipers; Manon Cw Spaander Journal: Cochrane Database Syst Rev Date: 2017-11-28
Authors: Harald Schmalenberg; Salah-Eddin Al-Batran; Claudia Pauligk; Thomas Zander; Alexander Reichart; Udo Lindig; Mathias Kleiß; Lothar Müller; Claus Bolling; Thomas Seufferlein; Peter Reichardt; Frank Kullmann; Henning Eschenburg; Alexander Schmittel; Matthias Egger; Andreas Block; Thorsten Oliver Goetze Journal: J Cancer Res Clin Oncol Date: 2017-12-28 Impact factor: 4.553
Authors: Haeseong Park; Ramon U Jin; Andrea Wang-Gillam; Rama Suresh; Caron Rigden; Manik Amin; Benjamin R Tan; Katrina S Pedersen; Kian-Huat Lim; Nikolaos A Trikalinos; Abhilasha Acharya; Megan L Copsey; Katherine A Navo; Ashley E Morton; Feng Gao; A Craig Lockhart Journal: JAMA Oncol Date: 2020-08-01 Impact factor: 31.777