Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Sökning: WFRF:(Pfeiffer Per) > Neoadjuvant FOLFIRI...

Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1) : a multicentre, randomised, phase 2 trial

Labori, Knut Jørgen (författare): Department of Hepato Pancreato Biliary Surgery, Oslo University Hospital ; Institute of Clinical Medicine, University of Oslo, Norway

Bratlie, Svein Olav (författare): Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden ; Department of Surgery, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Sweden

Andersson, Bodil (författare): Department of Clinical Sciences Lund, Surgery, Lund University, Sweden ; Skåne University Hospital, Lund, Sweden

visa fler...

Angelsen, Jon-Helge (författare): Department of Gastrointestinal Surgery, Haukeland University Hospital, Bergen, Norway ; Department of Clinical Medicine, University of Bergen, Norway

Biörserud, Christina (författare): Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden ; Department of Surgery, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Sweden

Björnsson, Bergthor (författare): Department of Surgery in Linköping, Linköping University, Sweden ; Department of Biomedical and Clinical Sciences, Linköping University, Sweden

Bringeland, Erling Audun (författare): Department of Gastrointestinal Surgery, St Olavs Hospital, Trondheim University Hospital, Norway ; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway

Elander, Nils (författare): Department of Biomedical and Clinical Sciences, Linköping University, Sweden ; Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, UK

Garresori, Herish (författare): Department of Hematology and Oncology, Stavanger University Hospital, Norway

Grønbech, Jon Erik (författare): Department of Gastrointestinal Surgery, St Olavs Hospital, Trondheim University Hospital, Norway ; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway

Haux, Johan (författare): Högskolan i Skövde,Institutionen för hälsovetenskaper,Forskningsmiljön hälsa, hållbarhet och digitalisering,Department of Oncology, Skaraborg Hospital Skövde, Sweden,Translational Medicine

Hemmingsson, Oskar (författare): Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Sweden ; Wallenberg Centre for Molecular Medicine, Umeå University, Sweden

Gustafsson Liljefors, Maria (författare): Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

Myklebust, Tor Åge (författare): Department of Registration, Cancer Registry of Norway, Oslo, Norway ; Department of Research and Innovation, Møre and Romsdal Hospital Trust, Ålesund, Norway

Nymo, Linn Såve (författare): Department of Gastrointestinal Surgery, University Hospital of North Norway, Tromsø, Norway ; Institute of Clinical Medicine, The Arctic University of Norway, Tromsø, Norway

Peltola, Katriina (författare): Comprehensive Cancer Center, Helsinki University Hospital, Finland

Pfeiffer, Per (författare): Department of Medical Oncology, Odense University Hospital, Denmark

Sallinen, Ville (författare): Gastroenterological Surgery/ Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Finland

Sandström, Per (författare): Department of Surgery in Linköping, Linköping University, Sweden ; Department of Biomedical and Clinical Sciences, Linköping University, Sweden

Sparrelid, Ernesto (författare): Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

Stenvold, Helge (författare): Department of Oncology, University Hospital of North Norway, Tromsø, Norway

Søreide, Kjetil (författare): Department of Clinical Medicine, University of Bergen, Norway ; Department of Gastrointestinal Surgery, Stavanger University Hospital, Norway

Tingstedt, Bobby (författare): Department of Clinical Sciences Lund, Surgery, Lund University and Skåne University Hospital, Lund, Sweden

Verbeke, Caroline (författare): Department of Pathology, Oslo University Hospital, Norway ; Institute of Clinical Medicine, University of Oslo, Norway

Öhlund, Daniel (författare): Wallenberg Centre for Molecular Medicine, Umeå University, Sweden ; Department of Radiation Sciences, Umeå University, Sweden

Klint, Leif (författare): Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden ; Department of Oncology, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Sweden

Dueland, Svein (författare): Department of Oncology, Oslo University Hospital, Norway

Lassen, Kristoffer (författare): Department of Hepato Pancreato Biliary Surgery, Oslo University Hospital, Norway ; Institute of Clinical Medicine, The Arctic University of Norway, Tromsø, Norway

Aahlin, Eirik Kjus (författare): Nordic Pancreatic Cancer Trial-1 study group

Bratthäll, Charlotte (författare): Nordic Pancreatic Cancer Trial-1 study group

Halimi, Asif (författare): Nordic Pancreatic Cancer Trial-1 study group

Hatlevoll, Ingunn (författare): Nordic Pancreatic Cancer Trial-1 study group

Heby, Margareta (författare): Nordic Pancreatic Cancer Trial-1 study group

Kokkola, Arto (författare): Nordic Pancreatic Cancer Trial-1 study group

Kordes, Maximilian (författare): Nordic Pancreatic Cancer Trial-1 study group

Lindblad, Stina (författare): Nordic Pancreatic Cancer Trial-1 study group

Lundgren, Linda (författare): Nordic Pancreatic Cancer Trial-1 study group

Mortensen, Michael Bau (författare): Nordic Pancreatic Cancer Trial-1 study group

Mortensen, Kim Erlend (författare): Nordic Pancreatic Cancer Trial-1 study group

Persson, Jan (författare): Nordic Pancreatic Cancer Trial-1 study group

Rangelova, Elena (författare): Nordic Pancreatic Cancer Trial-1 study group

Rønne, Elin (författare): Nordic Pancreatic Cancer Trial-1 study group

Sandvik, Oddvar Mathias (författare): Nordic Pancreatic Cancer Trial-1 study group

Søreide, Jon Arne (författare): Nordic Pancreatic Cancer Trial-1 study group

Vilhav, Caroline (författare): Nordic Pancreatic Cancer Trial-1 study group

Waardal, Kim (författare): Nordic Pancreatic Cancer Trial-1 study group

Wennerblom, Johanna (författare): Nordic Pancreatic Cancer Trial-1 study group

Williamsson, Caroline (författare): Nordic Pancreatic Cancer Trial-1 study group

Yaqub, Sheraz (författare): Nordic Pancreatic Cancer Trial-1 study group

visa färre...

(creator_code:org_t)

The Lancet Group, 2024
2024
Engelska.
Ingår i: The Lancet Gastroenterology & Hepatology. - : The Lancet Group. - 2468-1253. ; 9:3, s. 205-217

Relaterad länk:: https://urn.kb.se/re...; visa fler...; https://doi.org/10.1...; visa färre...

Tidskriftsartikel (refereegranskat)

Abstract Ämnesord

Stäng

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.

Hitta via bibliotek

The Lancet Gastroenterology & Hepatology (Sök värdpublikationen i LIBRIS)

Till lärosätets databas

Hitta mer i SwePub

Av författaren/redakt...: Labori, Knut Jør ...; Bratlie, Svein O ...; Andersson, Bodil; Angelsen, Jon-He ...; Biörserud, Chris ...; Björnsson, Bergt ...; visa fler...; Bringeland, Erli ...; Elander, Nils; Garresori, Heris ...; Grønbech, Jon Er ...; Haux, Johan; Hemmingsson, Osk ...; Gustafsson Lilje ...; Myklebust, Tor Å ...; Nymo, Linn Såve; Peltola, Katriin ...; Pfeiffer, Per; Sallinen, Ville; Sandström, Per; Sparrelid, Ernes ...; Stenvold, Helge; Søreide, Kjetil; Tingstedt, Bobby; Verbeke, Carolin ...; Öhlund, Daniel; Klint, Leif; Dueland, Svein; Lassen, Kristoff ...; Aahlin, Eirik Kj ...; Bratthäll, Charl ...; Halimi, Asif; Hatlevoll, Ingun ...; Heby, Margareta; Kokkola, Arto; Kordes, Maximili ...; Lindblad, Stina; Lundgren, Linda; Mortensen, Micha ...; Mortensen, Kim E ...; Persson, Jan; Rangelova, Elena; Rønne, Elin; Sandvik, Oddvar ...; Søreide, Jon Arn ...; Vilhav, Caroline; Waardal, Kim; Wennerblom, Joha ...; Williamsson, Car ...; Yaqub, Sheraz; visa färre...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Kirurgi

Artiklar i publikationen: The Lancet Gastr ...

Av lärosätet: Högskolan i Skövde

Sök utanför SwePub

Sök vidare i:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se

Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1) : a multicentre, randomised, phase 2 trial

Ämnesord

Nyckelord

Publikations- och innehållstyp

Hitta via bibliotek

Till lärosätets databas

Hitta mer i SwePub

Sök utanför SwePub