Tim Meyer1, Wendi Qian2, Martyn E Caplin3, Graham Armstrong4, Si-Houy Lao-Sirieix4, Richard Hardy4, Juan W Valle5, Denis C Talbot6, David Cunningham7, Nick Reed8, Ashley Shaw9, Shaunak Navalkissoor3, Tu-Vinh Luong3, Pippa G Corrie10. 1. Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, London, UK; UCL Cancer Institute, London, UK. 2. Cambridge Cancer Trials Centre, Cambridge Clinical Trials Unit - Cancer Theme, Addenbrooke's Hospital, Cambridge, UK; Medical Research Council Biostatistics Unit Hub for Trials Methodology, Cambridge, UK. 3. Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, London, UK. 4. Cambridge Cancer Trials Centre, Cambridge Clinical Trials Unit - Cancer Theme, Addenbrooke's Hospital, Cambridge, UK. 5. Department of Medical Oncology, The Christie, Manchester, UK. 6. Oxford Neuroendocrine Tumour Centre, Churchill Hospital, Oxford, UK. 7. Gastrointestinal Unit, The Royal Marsden, London, UK. 8. Beatson Oncology Centre, Glasgow, UK. 9. Oncology Centre, Addenbrooke's Hospital, Cambridge, UK. 10. Cambridge Cancer Trials Centre, Cambridge Clinical Trials Unit - Cancer Theme, Addenbrooke's Hospital, Cambridge, UK; Oncology Centre, Addenbrooke's Hospital, Cambridge, UK. Electronic address: pippa.corrie@addenbrookes.nhs.uk.
Abstract
BACKGROUND: Cytotoxic chemotherapy is widely used for advanced, unresectable pancreatic and other gastrointestinal foregut neuroendocrine tumours (NETs) and the most commonly used regimen combines 5-fluorouracil with streptozocin. The NET01 trial was designed to investigate whether capecitabine combined with streptozocin was an acceptable regimen with or without adding cisplatin. METHODS: Patients with advanced, unresectable NETs of pancreatic, gastrointestinal foregut or unknown primary site were randomised to receive three-weekly capecitabine (Cap) 625 mg/m(2) twice daily orally, streptozocin (Strep) 1.0 g/m(2) intravenously on day 1, with or without cisplatin (Cis) 70 mg/m(2) intravenously on day 1. The primary outcome measure was objective response. Secondary outcome measures included progression-free and overall survival, quality of life, toxicity and biochemical response. RESULTS: 86 (44 CapStrep, 42 CapStrepCis) patients were randomised. Best objective response rate was 12% (95% confidence interval (CI)=2-22%) with CapStrep and 16% (95% CI=4-27.4%) with CapStrepCis. Disease-control rate was 80% with CapStrep and 74% with CapStrepCis. The estimated median progression-free and overall survival were 10.2 and 26.7 months for CapStrep and 9.7 and 27.5 months for CapStrepCis. 44% of CapStrep and 68% of CapStrepCis patients experienced grade ≥3 adverse events. INTERPRETATION: The efficacies of the novel CapStrep±Cis regimens were very similar. CapStrep was better tolerated than CapStrepCis. The trial was registered as EudraCT: 2004-005202-71 and ISRCTN: 35124268.
BACKGROUND: Cytotoxic chemotherapy is widely used for advanced, unresectable pancreatic and other gastrointestinal foregut neuroendocrine tumours (NETs) and the most commonly used regimen combines 5-fluorouracil with streptozocin. The NET01 trial was designed to investigate whether capecitabine combined with streptozocin was an acceptable regimen with or without adding cisplatin. METHODS: Patients with advanced, unresectable NETs of pancreatic, gastrointestinal foregut or unknown primary site were randomised to receive three-weekly capecitabine (Cap) 625 mg/m(2) twice daily orally, streptozocin (Strep) 1.0 g/m(2) intravenously on day 1, with or without cisplatin (Cis) 70 mg/m(2) intravenously on day 1. The primary outcome measure was objective response. Secondary outcome measures included progression-free and overall survival, quality of life, toxicity and biochemical response. RESULTS: 86 (44 CapStrep, 42 CapStrepCis) patients were randomised. Best objective response rate was 12% (95% confidence interval (CI)=2-22%) with CapStrep and 16% (95% CI=4-27.4%) with CapStrepCis. Disease-control rate was 80% with CapStrep and 74% with CapStrepCis. The estimated median progression-free and overall survival were 10.2 and 26.7 months for CapStrep and 9.7 and 27.5 months for CapStrepCis. 44% of CapStrep and 68% of CapStrepCis patients experienced grade ≥3 adverse events. INTERPRETATION: The efficacies of the novel CapStrep±Cis regimens were very similar. CapStrep was better tolerated than CapStrepCis. The trial was registered as EudraCT: 2004-005202-71 and ISRCTN: 35124268.
Authors: Martin A Walter; Cédric Nesti; Marko Spanjol; Attila Kollár; Lukas Bütikofer; Viktoria L Gloy; Rebecca A Dumont; Christian A Seiler; Emanuel R Christ; Piotr Radojewski; Matthias Briel; Reto M Kaderli Journal: Cochrane Database Syst Rev Date: 2021-11-25
Authors: Reto M Kaderli; Marko Spanjol; Attila Kollár; Lukas Bütikofer; Viktoria Gloy; Rebecca A Dumont; Christian A Seiler; Emanuel R Christ; Piotr Radojewski; Matthias Briel; Martin A Walter Journal: JAMA Oncol Date: 2019-04-01 Impact factor: 31.777
Authors: Paula Espinosa-Olarte; Anna La Salvia; Maria C Riesco-Martinez; Beatriz Anton-Pascual; Rocio Garcia-Carbonero Journal: Rev Endocr Metab Disord Date: 2021-04-11 Impact factor: 9.306
Authors: Matthew H Wong; David L Chan; Adrian Lee; Bob T Li; Sumit Lumba; Stephen J Clarke; Jaswinder Samra; Nick Pavlakis Journal: PLoS One Date: 2016-06-30 Impact factor: 3.240
Authors: Caroline Martini; Eva-Maria Gamper; Lisa Wintner; Bernhard Nilica; Barbara Sperner-Unterweger; Bernhard Holzner; Irene Virgolini Journal: Health Qual Life Outcomes Date: 2016-09-10 Impact factor: 3.186