Fixed-dose rate gemcitabine alone or alternating with FOLFIRI.3 (irinotecan,leucovorin and fluorouracil) in the first-line treatment of patients with metastatic pancreatic adenocarcinoma: An AGEO randomised phase II study (FIRGEM) |
| |
| Institution: | 1. Hôpital Européen Georges Pompidou, Université Paris Descartes, Paris, France;2. CHU Jean Minjoz, Besançon, France;3. Gustave Roussy, Villejuif, France;4. Hôpital Privé Jean Mermoz, Lyon, France;5. Centre Georges-François Leclerc, Dijon, France;6. CHU de Tours-Hôpital Trousseau, Chambray-Les-Tours, France;7. CHU Avicenne, Université Paris 13, Sorbonne Paris Cité, Bobigny, France;8. CHU Bicêtre, Le Kremlin-Bicêtre, France;9. CHU Bichat-Claude Bernard, Paris, France;10. CHU Antoine Béclère, Clamart, France;11. Centre Hospitalier René Dubos, Cergy-Pontoise, France;1. Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China;2. Department of Laboratory Animal Science, Kunming Medical University, Kunming, Yunnan 650500, China;3. Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China;4. Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China;5. Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500, China;1. Department of Hematology, Cancer Center Amsterdam (CCA), VU University Medical Center, Amsterdam, The Netherlands;2. Department of Biostatistics, Cancer Center Amsterdam (CCA), VU University Medical Center, Amsterdam, The Netherlands;1. Department of Obstetrics and Gynecology, National Taiwan University, Taipei, Taiwan;2. Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;3. Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan;4. Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan;5. Department of Obstetrics and Gynecology, National Yang-Ming University, Taipei, Taiwan;6. Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan;7. Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan;8. Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Cheng Kung University, Tainan, Taiwan;9. Department of Obstetrics and Gynecology, Chi-Mei Medical Center, Tainan, Taiwan;10. Gynecologic Cancer Center, Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei, Taiwan;11. Fu Jen Catholic University, Hsinchuang, New Taipei City, Taiwan;12. Department of Obstetrics and Gynecology, Tri-Service General Hospital,National Defense Medical Center, Taipei, Taiwan;1. The Gade Laboratory of Pathology, Department of Clinical Medicine, University of Bergen, Norway;2. Department of Oral Surgery, Institute of Clinical Dentistry, University of Bergen, Norway;3. Department of Ear-Nose-and-Throat, Haukeland University Hospital, Bergen, Norway;4. Department of Pathology, Haukeland University Hospital, Bergen, Norway;5. Department of Biomedicine, University of Bergen, Norway;6. Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway;1. Department of Medicine, Division of Hematology/Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA;2. LBI-ACR VIEnna & ACR-ITR VIEnna, Center for Oncology and Haematology, Kaiser Franz Josef-Spital, Vienna, Austria;3. Centro Integral Oncologico Clara Campal, Universidad CEU San Pablo, Madrid, Spain;4. St. James’s Institute of Oncology, Leeds, UK;5. Department of Medicine, Division of Hematology–Oncology, University of California, San Diego, San Diego, CA, USA;6. Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA;7. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA;8. Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy;9. Division of Medical Oncology, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, USA;10. Department of Medicine, University of Chicago, Chicago, IL, USA;11. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA;12. Novartis Pharma AG, Basel, Switzerland;1. Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Department of Medical Oncology and Hematology, Berlin, Germany;2. Universitätsklinikum Hamburg-Eppendorf, Department of Medical Oncology, Hamburg, Germany;3. University of Göttingen, Department of General, Visceral and Pediatric Surgery, Göttingen, Germany;4. Sana Klinikum Lichtenberg, Department of General and Visceral Surgery, Berlin, Germany;5. Otto-Guericke-University of Magdeburg, Department of General, Visceral and Vascular Surgery, Magdeburg, Germany;6. University of Köln, Department of Gastroenterology and Hepatology, Köln, Germany;7. Universitätskliniken des Saarlandes, Department of Internal Medicine, Gastroenterology and Endocrinology, Homburg, Germany;8. Ernst von Bergmann Klinikum, Department of Hematology, Oncology and Palliative Care, Potsdam, Germany;9. Universitätsklinikum Frankfurt, Department of General and Visceral Surgery, Frankfurt, Germany;10. Eberhard-Karls-Universität Tübingen, Department of Internal Medicine, Tübingen, Germany;11. Marienhospital Stuttgart, Department of Hematology, Oncology and Palliative Care, Stuttgart Germany;12. Universitätsklinikum Mannheim, Department of Medical Oncology, Mannheim, Germany;13. Universitätsklinikum Jena, Department of Hematology and Oncology, Jena, Germany;14. CCRC, Düsseldorf, Germany;15. Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Department of Surgery, Berlin, Germany;p. Outpatient Department of Hematology/Oncology, Friedrichshafen, Germany |
| |
| Abstract: | BackgroundFluorouracil and irinotecan-based, and gemcitabine-based regimens, are the standard of care in the first-line treatment of patients with metastatic pancreatic cancer. New approaches are needed to improve survival and quality of life. Whether a sequential approach alternating irinotecan, fluorouracil and gemcitabine may be effective and tolerable in patients with metastatic pancreatic cancer is unknown.MethodsIn this randomised, multicentre, open-label, phase 2 trial, patients with metastatic pancreatic adenocarcinoma, World Health Organisation (WHO) performance status 0–1, and bilirubin levels <1.5 upper limit of normal values (ULN) were randomised 1:1 to receive as first-line treatment either FOLFIRI.3 (irinotecan, leucovorin and fluorouracil) alternating with fixed-dose rate gemcitabine as 2-month periods (FIRGEM, arm A), or fixed-dose rate gemcitabine alone (arm B). Treatment was continued until disease progression or limiting toxicity. The primary end-point was the crude progression-free survival (PFS) rate at 6 months. The study is registered with EudraCT (N° 2006-005703-34).ResultsBetween October 2007 and March 2011, 98 patients were enroled. The observed 6-month PFS rate was 43.5% (95% confidence interval (CI), 28.6–58.4%]) in arm A reaching the Fleming decision rules criteria to reject H0 and 26.1% (95% CI 12.9–39.3%]) in arm B.Objective response rates were 37% (23–51%) in arm A and 10% (1–19%) in arm B. Median PFS (5.0 versus 3.4 months, hazard ratio (HR) = 0.59 0.38–0.90]) and overall survival (11.0 versus 8.2 months, HR = 0.71 0.46–1.10]) were higher in arm A compared to arm B. The most frequent grade 3–4 toxicities were neutropenia (49%/24%; febrile neutropenia, 4%/0% in arms A/B), diarrhoea (arm A, 12% and arm B, 0%), and nausea/vomiting (8%/4%). No toxic deaths occurred.ConclusionThe FIRGEM strategy appears to be effective and feasible in patients with metastatic pancreatic cancer. |
| |
| Keywords: | Sequential chemotherapy Pancreatic cancer FOLFIRI 3 |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
