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Sökning: WFRF:(Williamsson Caroline) > Neoadjuvant FOLFIRI...

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FältnamnIndikatorerMetadata
00014405naa a2200913 4500
001oai:DiVA.org:his-23602
003SwePub
008240215s2024 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-236022 URI
0247 a https://doi.org/10.1016/s2468-1253(23)00405-32 DOI
040 a (SwePub)his
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Labori, Knut Jørgenu Department of Hepato Pancreato Biliary Surgery, Oslo University Hospital ; Institute of Clinical Medicine, University of Oslo, Norway4 aut
2451 0a Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1) :b a multicentre, randomised, phase 2 trial
264 1b The Lancet Group,c 2024
338 a print2 rdacarrier
500 a Correspondence to: Prof Knut Jørgen Labori, Department of Hepato Pancreato Biliary Surgery, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, N-0372 Oslo, NorwayFunding: Norwegian Cancer Society, South Eastern Norwegian Health Authority, The Sjöberg Foundation, and Helsinki University Hospital Research Grants.
520 a BackgroundIn patients undergoing resection for pancreatic cancer, adjuvant modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) improves overall survival compared with alternative chemotherapy regimens. We aimed to compare the efficacy and safety of neoadjuvant FOLFIRINOX with the standard strategy of upfront surgery in patients with resectable pancreatic ductal adenocarcinoma.MethodsNORPACT-1 was a multicentre, randomised, phase 2 trial done in 12 hospitals in Denmark, Finland, Norway, and Sweden. Eligible patients were aged 18 years or older, with a WHO performance status of 0 or 1, and had a resectable tumour of the pancreatic head radiologically strongly suspected to be pancreatic adenocarcinoma. Participants were randomly assigned (3:2 before October, 2018, and 1:1 after) to the neoadjuvant FOLFIRINOX group or upfront surgery group. Patients in the neoadjuvant FOLFIRINOX group received four neoadjuvant cycles of FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and fluorouracil 400 mg/m2 bolus then 2400 mg/m2 over 46 h on day 1 of each 14-day cycle), followed by surgery and adjuvant chemotherapy. Patients in the upfront surgery group underwent surgery and then received adjuvant chemotherapy. Initially, adjuvant chemotherapy was gemcitabine plus capecitabine (gemcitabine 1000 mg/m2 over 30 min on days 1, 8, and 15 of each 28-day cycle and capecitabine 830 mg/m2 twice daily for 3 weeks with 1 week of rest in each 28-day cycle; four cycles in the neoadjuvant FOLFIRINOX group, six cycles in the upfront surgery group). A protocol amendment was subsequently made to permit use of adjuvant modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2400 mg/m2 over 46 h on day 1 of each 14-day cycle; eight cycles in the neoadjuvant FOLFIRINOX group, 12 cycles in the upfront surgery group). Randomisation was performed with a computerised algorithm that stratified for each participating centre and used a concealed block size of two to six. Patients, investigators, and study team members were not masked to treatment allocation. The primary endpoint was overall survival at 18 months. Analyses were done in the intention-to-treat (ITT) and per-protocol populations. Safety was assessed in all patients who were randomly assigned and received at least one cycle of neoadjuvant or adjuvant therapy. This trial is registered with ClinicalTrials.gov, NCT02919787, and EudraCT, 2015-001635-21, and is ongoing.FindingsBetween Feb 8, 2017, and April 21, 2021, 77 patients were randomly assigned to receive neoadjuvant FOLFIRINOX and 63 to undergo upfront surgery. All patients were included in the ITT analysis. For the per-protocol analysis, 17 (22%) patients were excluded from the neoadjuvant FOLFIRINOX group (ten did not receive neoadjuvant therapy, four did not have pancreatic ductal adenocarcinoma, and three received another neoadjuvant regimen), and eight (13%) were excluded from the upfront surgery group (seven did not have pancreatic ductal adenocarcinoma and one did not undergo surgical exploration). 61 (79%) of 77 patients in the neoadjuvant FOLFIRINOX group received neoadjuvant therapy. The proportion of patients alive at 18 months by ITT was 60% (95% CI 49–71) in the neoadjuvant FOLFIRINOX group versus 73% (62–84) in the upfront surgery group (p=0·032), and median overall survival by ITT was 25·1 months (95% CI 17·2–34·9) versus 38·5 months (27·6–not reached; hazard ratio [HR] 1·52 [95% CI 1·00–2·33], log-rank p=0·050). The proportion of patients alive at 18 months in per-protocol analysis was 57% (95% CI 46–67) in the neoadjuvant FOLFIRINOX group versus 70% (55–83) in the upfront surgery group (p=0·14), and median overall survival in per-protocol population was 23·0 months (95% CI 16·2–34·9) versus 34·4 months (19·4–not reached; HR 1·46 [95% CI 0·99–2·17], log-rank p=0·058). In the safety population, 42 (58%) of 73 patients in the neoadjuvant FOLFIRINOX group and 19 (40%) of 47 patients in the upfront surgery group had at least one grade 3 or worse adverse event. 63 (82%) of 77 patients in the neoadjuvant group and 56 (89%) of 63 patients in the upfront surgery group had resection (p=0·24). One sudden death of unknown cause and one COVID-19-related death occurred after the first cycle of neoadjuvant FOLFIRINOX. Adjuvant chemotherapy was initiated in 51 (86%) of 59 patients with resected pancreatic ductal adenocarcinoma in the neoadjuvant FOLFIRINOX group and 44 (90%) of 49 patients with resected pancreatic ductal adenocarcinoma in the upfront surgery group (p=0·56). Adjuvant modified FOLFIRINOX was given to 13 (25%) patients in the neoadjuvant FOLFIRINOX group and 19 (43%) patients in the upfront surgery group. During adjuvant chemotherapy, neutropenia (11 [22%] patients in the neoadjuvant FOLFIRINOX group and five [11%] in the upfront surgery group) was the most common grade 3 or worse adverse event.InterpretationThis phase 2 trial did not show a survival benefit from neoadjuvant FOLFIRINOX in resectable pancreatic ductal adenocarcinoma compared with upfront surgery. Implementation of neoadjuvant FOLFIRINOX was challenging. Future trials on treatment sequencing in resectable pancreatic ductal adenocarcinoma should be biomarker driven.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Kirurgi0 (SwePub)302122 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Surgery0 (SwePub)302122 hsv//eng
653 a Translationell medicin TRIM
653 a Translational Medicine TRIM
7001 a Bratlie, Svein Olavu Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden ; Department of Surgery, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Sweden4 aut
7001 a Andersson, Bodilu Department of Clinical Sciences Lund, Surgery, Lund University, Sweden ; Skåne University Hospital, Lund, Sweden4 aut
7001 a Angelsen, Jon-Helgeu Department of Gastrointestinal Surgery, Haukeland University Hospital, Bergen, Norway ; Department of Clinical Medicine, University of Bergen, Norway4 aut
7001 a Biörserud, Christinau Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden ; Department of Surgery, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Sweden4 aut
7001 a Björnsson, Bergthoru Department of Surgery in Linköping, Linköping University, Sweden ; Department of Biomedical and Clinical Sciences, Linköping University, Sweden4 aut
7001 a Bringeland, Erling Audunu Department of Gastrointestinal Surgery, St Olavs Hospital, Trondheim University Hospital, Norway ; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway4 aut
7001 a Elander, Nilsu Department of Biomedical and Clinical Sciences, Linköping University, Sweden ; Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, UK4 aut
7001 a Garresori, Herishu Department of Hematology and Oncology, Stavanger University Hospital, Norway4 aut
7001 a Grønbech, Jon Eriku Department of Gastrointestinal Surgery, St Olavs Hospital, Trondheim University Hospital, Norway ; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway4 aut
7001 a Haux, Johanu Högskolan i Skövde,Institutionen för hälsovetenskaper,Forskningsmiljön hälsa, hållbarhet och digitalisering,Department of Oncology, Skaraborg Hospital Skövde, Sweden,Translational Medicine4 aut0 (Swepub:his)hauj
7001 a Hemmingsson, Oskaru Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Sweden ; Wallenberg Centre for Molecular Medicine, Umeå University, Sweden4 aut
7001 a Gustafsson Liljefors, Mariau Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden4 aut
7001 a Myklebust, Tor Ågeu Department of Registration, Cancer Registry of Norway, Oslo, Norway ; Department of Research and Innovation, Møre and Romsdal Hospital Trust, Ålesund, Norway4 aut
7001 a Nymo, Linn Såveu Department of Gastrointestinal Surgery, University Hospital of North Norway, Tromsø, Norway ; Institute of Clinical Medicine, The Arctic University of Norway, Tromsø, Norway4 aut
7001 a Peltola, Katriinau Comprehensive Cancer Center, Helsinki University Hospital, Finland4 aut
7001 a Pfeiffer, Peru Department of Medical Oncology, Odense University Hospital, Denmark4 aut
7001 a Sallinen, Villeu Gastroenterological Surgery/ Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Finland4 aut
7001 a Sandström, Peru Department of Surgery in Linköping, Linköping University, Sweden ; Department of Biomedical and Clinical Sciences, Linköping University, Sweden4 aut
7001 a Sparrelid, Ernestou Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden4 aut
7001 a Stenvold, Helgeu Department of Oncology, University Hospital of North Norway, Tromsø, Norway4 aut
7001 a Søreide, Kjetilu Department of Clinical Medicine, University of Bergen, Norway ; Department of Gastrointestinal Surgery, Stavanger University Hospital, Norway4 aut
7001 a Tingstedt, Bobbyu Department of Clinical Sciences Lund, Surgery, Lund University and Skåne University Hospital, Lund, Sweden4 aut
7001 a Verbeke, Carolineu Department of Pathology, Oslo University Hospital, Norway ; Institute of Clinical Medicine, University of Oslo, Norway4 aut
7001 a Öhlund, Danielu Wallenberg Centre for Molecular Medicine, Umeå University, Sweden ; Department of Radiation Sciences, Umeå University, Sweden4 aut
7001 a Klint, Leifu Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden ; Department of Oncology, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Sweden4 aut
7001 a Dueland, Sveinu Department of Oncology, Oslo University Hospital, Norway4 aut
7001 a Lassen, Kristofferu Department of Hepato Pancreato Biliary Surgery, Oslo University Hospital, Norway ; Institute of Clinical Medicine, The Arctic University of Norway, Tromsø, Norway4 aut
7001 a Aahlin, Eirik Kjusu Nordic Pancreatic Cancer Trial-1 study group4 aut
7001 a Bratthäll, Charlotteu Nordic Pancreatic Cancer Trial-1 study group4 aut
7001 a Halimi, Asifu Nordic Pancreatic Cancer Trial-1 study group4 aut
7001 a Hatlevoll, Ingunnu Nordic Pancreatic Cancer Trial-1 study group4 aut
7001 a Heby, Margaretau Nordic Pancreatic Cancer Trial-1 study group4 aut
7001 a Kokkola, Artou Nordic Pancreatic Cancer Trial-1 study group4 aut
7001 a Kordes, Maximilianu Nordic Pancreatic Cancer Trial-1 study group4 aut
7001 a Lindblad, Stinau Nordic Pancreatic Cancer Trial-1 study group4 aut
7001 a Lundgren, Lindau Nordic Pancreatic Cancer Trial-1 study group4 aut
7001 a Mortensen, Michael Bauu Nordic Pancreatic Cancer Trial-1 study group4 aut
7001 a Mortensen, Kim Erlendu Nordic Pancreatic Cancer Trial-1 study group4 aut
7001 a Persson, Janu Nordic Pancreatic Cancer Trial-1 study group4 aut
7001 a Rangelova, Elenau Nordic Pancreatic Cancer Trial-1 study group4 aut
7001 a Rønne, Elinu Nordic Pancreatic Cancer Trial-1 study group4 aut
7001 a Sandvik, Oddvar Mathiasu Nordic Pancreatic Cancer Trial-1 study group4 aut
7001 a Søreide, Jon Arneu Nordic Pancreatic Cancer Trial-1 study group4 aut
7001 a Vilhav, Carolineu Nordic Pancreatic Cancer Trial-1 study group4 aut
7001 a Waardal, Kimu Nordic Pancreatic Cancer Trial-1 study group4 aut
7001 a Wennerblom, Johannau Nordic Pancreatic Cancer Trial-1 study group4 aut
7001 a Williamsson, Carolineu Nordic Pancreatic Cancer Trial-1 study group4 aut
7001 a Yaqub, Sherazu Nordic Pancreatic Cancer Trial-1 study group4 aut
7102 a Department of Hepato Pancreato Biliary Surgery, Oslo University Hospital ; Institute of Clinical Medicine, University of Oslo, Norwayb Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden ; Department of Surgery, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Sweden4 org
7730 t The Lancet Gastroenterology & Hepatologyd : The Lancet Groupg 9:3, s. 205-217q 9:3<205-217x 2468-1253
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-23602
8564 8u https://doi.org/10.1016/s2468-1253(23)00405-3

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