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Pancreatic Neoplasms: HELP
Articles by Thierry Conroy
Based on 20 articles published since 2008
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Between 2008 and 2019, T. Conroy wrote the following 20 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Guideline Consensus statement on mandatory measurements in pancreatic cancer trials (COMM-PACT) for systemic treatment of unresectable disease. 2018

Ter Veer, Emil / van Rijssen, L Bengt / Besselink, Marc G / Mali, Rosa M A / Berlin, Jordan D / Boeck, Stefan / Bonnetain, Franck / Chau, Ian / Conroy, Thierry / Van Cutsem, Eric / Deplanque, Gael / Friess, Helmut / Glimelius, Bengt / Goldstein, David / Herrmann, Richard / Labianca, Roberto / Van Laethem, Jean-Luc / Macarulla, Teresa / van der Meer, Jonathan H M / Neoptolemos, John P / Okusaka, Takuji / O'Reilly, Eileen M / Pelzer, Uwe / Philip, Philip A / van der Poel, Marcel J / Reni, Michele / Scheithauer, Werner / Siveke, Jens T / Verslype, Chris / Busch, Olivier R / Wilmink, Johanna W / van Oijen, Martijn G H / van Laarhoven, Hanneke W M. ·Department of Medical Oncology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, Netherlands. · Department of Surgery, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, Netherlands. · Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA. · Department of Internal Medicine III, Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany. · Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France. · Royal Marsden NHS Foundation Trust, London and Surrey, UK. · Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, Vandoeuvre-lès-Nancy, France. · Department of Gastroenterology and Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium. · Department of Oncology, Hôpital Riviera-Chablais, Vevey, Switzerland. · Department of Surgery, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany. · Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. · Nelune Cancer Centre, Prince of Wales Hospital, Prince of Wales Clinical School University of New South Wales, Randwick, NSW, Australia. · Department of Medical Oncology, University Hospital Basel, Basel, Switzerland. · Cancer Center, ASST Papa Giovanni XXIII, Bergamo, Italy. · Department of Gastroenterology, Gastrointestinal Cancer Unit, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. · Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. · Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. · Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA. · Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany; Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany. · Department of Oncology, Karmanos Cancer Center, Wayne State University, Detroit, MI, USA. · Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Internal Medicine I, Medical University Vienna, Vienna, Austria. · Division of Solid Tumor Translational Oncology, West German Cancer Cancer, University Hospital Essen, Essen, Germany; German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany. · Department of Digestive Oncology, University Hospitals Leuven, Leuven, Belgium. · Department of Medical Oncology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, Netherlands. Electronic address: h.vanlaarhoven@amc.uva.nl. ·Lancet Oncol · Pubmed #29508762.

ABSTRACT: Variations in the reporting of potentially confounding variables in studies investigating systemic treatments for unresectable pancreatic cancer pose challenges in drawing accurate comparisons between findings. In this Review, we establish the first international consensus on mandatory baseline and prognostic characteristics in future trials for the treatment of unresectable pancreatic cancer. We did a systematic literature search to find phase 3 trials investigating first-line systemic treatment for locally advanced or metastatic pancreatic cancer to identify baseline characteristics and prognostic variables. We created a structured overview showing the reporting frequencies of baseline characteristics and the prognostic relevance of identified variables. We used a modified Delphi panel of two rounds involving an international panel of 23 leading medical oncologists in the field of pancreatic cancer to develop a consensus on the various variables identified. In total, 39 randomised controlled trials that had data on 15 863 patients were included, of which 32 baseline characteristics and 26 prognostic characteristics were identified. After two consensus rounds, 23 baseline characteristics and 12 prognostic characteristics were designated as mandatory for future pancreatic cancer trials. The COnsensus statement on Mandatory Measurements in unresectable PAncreatic Cancer Trials (COMM-PACT) identifies a mandatory set of baseline and prognostic characteristics to allow adequate comparison of outcomes between pancreatic cancer studies.

2 Guideline Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials). 2014

Bonnetain, Franck / Bonsing, Bert / Conroy, Thierry / Dousseau, Adelaide / Glimelius, Bengt / Haustermans, Karin / Lacaine, François / Van Laethem, Jean Luc / Aparicio, Thomas / Aust, Daniela / Bassi, Claudio / Berger, Virginie / Chamorey, Emmanuel / Chibaudel, Benoist / Dahan, Laeticia / De Gramont, Aimery / Delpero, Jean Robert / Dervenis, Christos / Ducreux, Michel / Gal, Jocelyn / Gerber, Erich / Ghaneh, Paula / Hammel, Pascal / Hendlisz, Alain / Jooste, Valérie / Labianca, Roberto / Latouche, Aurelien / Lutz, Manfred / Macarulla, Teresa / Malka, David / Mauer, Muriel / Mitry, Emmanuel / Neoptolemos, John / Pessaux, Patrick / Sauvanet, Alain / Tabernero, Josep / Taieb, Julien / van Tienhoven, Geertjan / Gourgou-Bourgade, Sophie / Bellera, Carine / Mathoulin-Pélissier, Simone / Collette, Laurence. ·Methodology and Quality of Life Unit in Cancer, EA 3181, University Hospital of Besançon and CTD-INCa Gercor, UNICNCER GERICO, Besançon, France. Electronic address: franck.bonnetain@univ-fcomte.fr. · Leiden University Medical Center, Leiden, Netherlands. · Department of Medical Oncology, Institut de Cancérologie de Lorraine, Vandoeuvre-les-Nancy, France. · Bordeaux Segalen University & CHRU, Bordeaux, France. · Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden. · Department of Radiation Oncology, Leuven, Belgium. · Digestive Surgical Department, Tenon hospital, Paris, France. · Gastro Intestinal Cancer Unit Erasme Hospital Brussels, Belgium. · Gastroenterology Department, Avicenne Hospital, Paris 13, Bobigny, France. · Institute for Pathology, University Hospital Carl-Gustav-Carus, Dresden, Germany. · Surgical and Gastroenterological Department, Endocrine and Pancreatic Unit, Hospital of 'G.B.Rossi', University of Verona, Italy. · Institut de Cancérologie de l'Ouest - Centre Paul Papin Centre de Lutte Contre le Cancer (CLCC), Angers, France. · Biostatistics Unit, Centre Antoine Lacassagne, Nice, France. · Oncology Department, Hôpital Saint-Antoine & CTD-INCa GERCOR, Assistance Publique des Hôpitaux de Paris, UPMC Paris VI, Paris, France. · Gastroenterology Department, Hopital la Timone, Assitance publique des Hopitaux de Marseille, Marseille, France. · Department of Surgery, Institut Paoli Calmettes, Marseille, France. · Department of Surgery, Agia Olga Hospital, Athens, Greece. · Department of Gastroenterology, Institut Gustave Roussy, Villejuif, France. · Biostatistician, Biostatistics Unit, Centre Antoine Lacassagne, Nice, France. · Department of Radiotherapy, Institut fuer Radioonkologie, Vienna, Austria. · Department of Surgical Oncology, Royal Liverpool Hospital, United Kingdom. · Department of Gastroenterology, Beaujon Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France. · Digestive Oncology and Gastro-enterology Department, Jules Bordet Institute, Brussels, Belgium. · Digestive Cancer Registry, INSERM U866, Dijon, France. · Medical Oncology Unit, Ospedali Riuniti di Bergamo, Bergame, Italy. · Inserm, Centre for Research in Epidemiology and Population Health, U1018, Biostatistics Team, Villejuif, France. · Gastroenterology Department, Caritas Hospital, Saarbrücken, Germany. · Department of the Gastrointestinal Tumors and Phase I Unit, Vall d'Hebron University Hospital, Barcelona, Spain. · Statistics Department, EORTC, Brussels, Belgium. · Department of Medical Oncology, Institut Curie, Hôpital René Huguenin, Saint-Cloud, France. · Division of Surgery and Oncology at the University of Liverpool and Royal Liverpool University Hospital, Liverpool, United Kingdom. · Department of Digestive Surgery, Universitu Hospital Strasbourg, France. · Department of Hepato-pancreatic and Biliary Surgery, Beaujon Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France. · Department of Hepato-gastroenterology and Digestive Oncology, Georges Pompidou European hospital, Paris, France. · Department of Radiation Oncology, Academisch Medisch Centrum, Amsterdam, The Netherlands. · Institut Du Cancer de Montpellier, Comprehensive Cancer Centre, and Data Center for Cancer Clinical Trials, CTD-INCa, Montpellier, France. · Clinical and Epidemiological Research Unit, Institut Bergonie, Comprehensive Cancer Centre, Bordeaux, France; Data Center for Cancer Clinical Trials, CTD-INCa, Bordeaux, France; INSERM, Centre d'Investigation Clinique - Épidémiologie Clinique CIC-EC 7, F-33000 Bordeaux, France. ·Eur J Cancer · Pubmed #25256896.

ABSTRACT: BACKGROUND: Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. METHODS: Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). RESULTS: For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. CONCLUSION: The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.

3 Guideline New strategies and designs in pancreatic cancer research: consensus guidelines report from a European expert panel. 2012

Van Laethem, J-L / Verslype, C / Iovanna, J L / Michl, P / Conroy, T / Louvet, C / Hammel, P / Mitry, E / Ducreux, M / Maraculla, T / Uhl, W / Van Tienhoven, G / Bachet, J B / Maréchal, R / Hendlisz, A / Bali, M / Demetter, P / Ulrich, F / Aust, D / Luttges, J / Peeters, M / Mauer, M / Roth, A / Neoptolemos, J P / Lutz, M / Anonymous6430701. ·Gastrointestinal Cancer Unit, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. jl.vanlaethem@erasme.ulb.ac.be ·Ann Oncol · Pubmed #21810728.

ABSTRACT: Although the treatment of pancreatic ductal adenocarcinoma (PDAC) remains a huge challenge, it is entering a new era with the development of new strategies and trial designs. Because there is an increasing number of novel therapeutic agents and potential combinations available to test in patients with PDAC, the identification of robust prognostic and predictive markers and of new targets and relevant pathways is a top priority as well as the design of adequate trials incorporating molecular-driven hypothesis. We presently report a consensus strategy for research in pancreatic cancer that was developed by a multidisciplinary panel of experts from different European institutions and collaborative groups involved in pancreatic cancer. The expert panel embraces the concept of exploratory early proof of concept studies, based on the prediction of response to novel agents and combinations, and randomised phase II studies permitting the selection of the best therapeutic approach to go forward into phase III, where the recommended primary end point remains overall survival. Trials should contain as many translational components as possible, relying on standardised tissue and blood processing and robust biobanking, and including dynamic imaging. Attention should not only be paid to the pancreatic cancer cells but also to microenvironmental factors and stem/stellate cells.

4 Review Pancreatic cancer: French clinical practice guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, AFC). 2018

Neuzillet, Cindy / Gaujoux, Sébastien / Williet, Nicolas / Bachet, Jean-Baptiste / Bauguion, Lucile / Colson Durand, Laurianne / Conroy, Thierry / Dahan, Laetitia / Gilabert, Marine / Huguet, Florence / Marthey, Lysiane / Meilleroux, Julie / de Mestier, Louis / Napoléon, Bertrand / Portales, Fabienne / Sa Cunha, Antonio / Schwarz, Lilian / Taieb, Julien / Chibaudel, Benoist / Bouché, Olivier / Hammel, Pascal / Anonymous680992 / Anonymous690992 / Anonymous700992 / Anonymous710992 / Anonymous720992 / Anonymous730992 / Anonymous740992 / Anonymous750992 / Anonymous760992 / Anonymous770992. ·Department of Medical Oncology, Curie Institute, Versailles Saint-Quentin University (UVSQ), Saint-Cloud, France. Electronic address: cindy.neuzillet@gmail.com. · Department of Digestive, Hepato-Biliary and Pancreatic Surgery, Cochin Hospital, AP-HP, Paris Descartes Faculty of Medicine, Paris Descartes University, Sorbonne Paris Cité, Paris, France. · Hepato-Gastroenterology Department, University Hospital of Saint-Etienne, Saint Priest en Jarez, France. · Hepato-Gastroenterology Department, Pitié Salpétrière University Hospital, AP-HP, Paris Cedex 13, France. · Hepato-Gastroenterology Department, Departmental Hospital Center, La Roche sur Yon, France. · Department of Radiotherapy, Henri Mondor Hospital, AP-HP, Université Paris Est Creteil, Créteil, France. · Department of Medical Oncology, Lorraine Institute of Oncology and Lorraine University, Vandoeuvre-lès-Nancy Cedex, France. · Digestive Oncology Department, "DACCORD" (Digestif, Anatomie pathologique, Chirurgie, CISIH, Oncologie, Radiothérapie, Dermatologie) pole, CHU Timone, Marseille Cedex 05, France. · Paoli Calmettes Institute, Department of Medical Oncology and Cancer Research Center of Marseille (CRCM), INSERM U1068 Stress Cell, Aix-Marseille University, Marseille, France. · Department of Oncology and Radiotherapy, Tenon Hospital, East Paris University Hospitals, AP-HP, Paris Sorbonne University, Paris, France. · Gastroenterology Department, Béclère Hospital, AP-HP, Clamart, France. · Pathology Department, Toulouse University Hospital, Toulouse, France. · Department of Gastroenterology-Pancreatology, Beaujon Hospital, APHP, Paris 7 University, Clichy, France. · Jean Mermoz Private Hospital, Ramsay Générale de Santé, Lyon, France. · Digestive Oncology Department, Regional Institute of Cancer, Montpellier, France. · INSERM UMR 935, Paul Brousse Hospital, Hepatobiliary Center, AP-HP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France. · Department of Digestive Surgery, Hôpital Charles Nicolle, Rouen University Hospital, Rouen, France and Genomic and Personalized Medicine in Cancer and Neurological Disorders, UMR 1245 INSERM, Rouen University, France. · Hepato-Gastroenterology and Digestive Oncology Department, Georges Pompidou European Hospital, AP-HP, Paris, France. · Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France. · Hepato-Gastroenterology and Digestive Oncology Department, Robert Debré University Hospital, Avenue Général Koenig, 51092 Reims Cedex, France. · Department of Digestive Oncology, Beaujon University Hospital (AP-HP), Paris VII Diderot University, Clichy-la-Garenne, France. Electronic address: pascal.hammel@aphp.fr. ·Dig Liver Dis · Pubmed #30219670.

ABSTRACT: BACKGROUND: This document is a summary of the French intergroup guidelines regarding the management of pancreatic adenocarcinoma (PA), updated in July 2018. DESIGN: This collaborative work was produced under the auspices of all French medical and surgical societies involved in the management of PA. It is based on the previous guidelines, recent literature review and expert opinions. Recommendations were graded in three categories, according to the level of evidence. RESULTS: Over the last seven years, significant changes in PA management have been implemented in clinical practice. Imaging/staging: diffusion magnetic resonance imaging is useful before surgery to rule out small liver metastases. SURGERY: centralization of pancreatic surgery in expert centers is associated with a decreased postoperative mortality. Adjuvant chemotherapy: modified FOLFIRINOX in fit patients, or gemcitabine, or 5-FU, or gemcitabine plus capecitabine, to be discussed on a case-by-case basis. Locally advanced PA: no survival benefit of chemoradiotherapy. Metastatic PA: FOLFIRINOX and gemcitabine plus nab-paclitaxel combination are first-line standards in fit patients; second-line with 5FU/nal-IRI or 5FU/oxaliplatin combination after first-line gemcitabine. CONCLUSION: Guidelines for management of PA are continuously evolving and need to be regularly updated. This constant progress is made possible through clinical and translational research. However, as each individual case is particular, they cannot substitute to multidisciplinary tumor board discussion.

5 Review FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. 2016

Suker, Mustafa / Beumer, Berend R / Sadot, Eran / Marthey, Lysiane / Faris, Jason E / Mellon, Eric A / El-Rayes, Bassel F / Wang-Gillam, Andrea / Lacy, Jill / Hosein, Peter J / Moorcraft, Sing Yu / Conroy, Thierry / Hohla, Florian / Allen, Peter / Taieb, Julien / Hong, Theodore S / Shridhar, Ravi / Chau, Ian / van Eijck, Casper H / Koerkamp, Bas Groot. ·Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Hepatogastroenterology, Antoine Beclère Hospital, Assistance publique-Hôpitaux de Paris, Paris Sud University, Clamart, France. · Department of Hematology-Oncology, Massachusetts General Hospital, Boston, MA, USA. · Department of Radiation Oncology, H Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. · Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA. · Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA. · Department of Medicine, Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. · Department of Medicine, Division of Medical Oncology, University of Kentucky-Markey Cancer Center, Lexington, KY, USA. · Department of Medicine, The Royal Marsden National Health Service Foundation Trust, London and Surrey, UK. · Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, Vandoeuvre-lès-Nancy, France. · Department of Hematology, Medical Oncology, Hemostasis, Rheumatology and Infectious Diseases, Paracelsus Medical University of Salzburg, Salzburg, Austria. · Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, Assistance publique-Hôpitaux de Paris, Sorbonne Paris Cité, Paris Descartes University, Cancer Research Personalized Medicine (CARPEM), Paris, France. · Department of Radiation Oncology, Florida Hospital Cancer Institute, Orlando, FL, USA. · Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands. Electronic address: b.grootkoerkamp@erasmusmc.nl. ·Lancet Oncol · Pubmed #27160474.

ABSTRACT: BACKGROUND: 35% of patients with pancreatic cancer have unresectable locally advanced disease at diagnosis. Several studies have examined systemic chemotherapy with FOLFIRINOX (leucovorin and fluorouracil plus irinotecan and oxaliplatin) in patients with locally advanced pancreatic cancer. We aimed to assess the effectiveness of FOLFIRINOX as first-line treatment in this patient population. METHODS: We systematically searched Embase, MEDLINE (OvidSP), Web of Science, Scopus, PubMed Publisher, Cochrane, and Google Scholar from July 1, 1994, to July 2, 2015, for studies of treatment-naive patients of any age who received FOLFIRINOX as first-line treatment of locally advanced pancreatic cancer. Our primary outcome was overall survival. Secondary outcomes were progression-free survival; rates of grade 3 or 4 adverse events; and the proportion of patients who underwent radiotherapy or chemoradiotherapy, surgical resection after FOLFIRINOX, and R0 resection. We evaluated survival outcomes with the Kaplan-Meier method with patient-level data. Grade 3 or 4 adverse events, and the proportion of patients who underwent subsequent radiotherapy or chemoradiotherapy or resection, were pooled in a random-effects model. FINDINGS: We included 13 studies comprising 689 patients, of whom 355 (52%) patients had locally advanced pancreatic cancer. 11 studies, comprising 315 patients with locally advanced disease, reported survival outcomes and were eligible for patient-level meta-analysis. Median overall survival from the start of FOLFIRINOX ranged from 10·0 months (95% CI 4·0-16·0) to 32·7 months (23·1-42·3) across studies with a pooled patient-level median overall survival of 24·2 months (95% CI 21·7-26·8). Median progression-free survival ranged from 3·0 months (95% CI not calculable) to 20·4 months (6·5-34·3) across studies with a patient-level median progression-free survival of 15·0 months (95% 13·8-16·2). In ten studies comprising 490 patients, 296 grade 3 or 4 adverse events were reported (60·4 events per 100 patients). No deaths were attributed to FOLFIRINOX toxicity. The proportion of patients who underwent radiotherapy or chemoradiotherapy ranged from 31% to 100% across studies. In eight studies, 154 (57%) of 271 patients received radiotherapy or chemoradiotherapy after FOLFIRINOX. The pooled proportion of patients who received any radiotherapy treatment was 63·5% (95% CI 43·3-81·6, I(2) 90%). The proportion of patients who underwent surgical resection for locally advanced pancreatic cancer ranged from 0% to 43%. The proportion of patients who had R0 resection of those who underwent resection ranged from 50% to 100% across studies. In 12 studies, 91 (28%) of 325 patients underwent resection after FOLFIRINOX. The pooled proportion of patients who had resection was 25·9% (95% CI 20·2-31·9, I(2) 24%). R0 resection was reported in 60 (74%) of 81 patients. The pooled proportion of patients who had R0 resection was 78·4% (95% CI 60·2-92·2, I(2) 64%). INTERPRETATION: Patients with locally advanced pancreatic cancer treated with FOLFIRINOX had a median overall survival of 24·2 months-longer than that reported with gemcitabine (6-13 months). Future research should assess these promising results in a randomised controlled trial, and should establish which patients might benefit from radiotherapy or chemoradiotherapy or resection after FOLFIRINOX. FUNDING: None.

6 Review Current standards and new innovative approaches for treatment of pancreatic cancer. 2016

Conroy, Thierry / Bachet, Jean-Baptiste / Ayav, Ahmet / Huguet, Florence / Lambert, Aurélien / Caramella, Caroline / Maréchal, Raphaël / Van Laethem, Jean-Luc / Ducreux, Michel. ·Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, 6 avenue de Bourgogne, CS 30519, 54519, Vandoeuvre-lès-Nancy, France. Electronic address: t.conroy@nancy.unicancer.fr. · Department of Hepato-Gastroenterology, Pitié-Salpétrière University Hospital, 47-83 boulevard de l'hôpital, 75651, Paris Cedex 13, France. · Department of Surgery, Nancy University Hospital Lorraine and Lorraine University, rue du Morvan, 54511, Vandoeuvre-lès Nancy, France. · Department of Radiation Therapy, Tenon Hospital, Paris Est University Hospitals, 4 rue de la Chine, 75020, Paris, France. · Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, 6 avenue de Bourgogne, CS 30519, 54519, Vandoeuvre-lès-Nancy, France. · Gustave Roussy Cancer Campus Grand Paris, 114 rue Edouard-Vaillant, 94805, Villejuif Cedex, France. · Department of Gastroenterology, Erasme University Hospital-ULB-Brussels, Lennikstreet 808, 1070, Brussels, Belgium. ·Eur J Cancer · Pubmed #26851397.

ABSTRACT: Pancreatic adenocarcinoma remains a devastating disease with a 5-year survival rate not exceeding 6%. Treatment of this disease remains a major challenge. This article reviews the state-of-the-art in the management of this disease and the new innovative approaches that may help to accelerate progress in treating its victims. After careful pre-therapeutic evaluation, only 15-20% of patients diagnosed with a pancreatic cancer (PC) are eligible for upfront radical surgery. After R0 or R1 resection in such patients, evidence suggests a significantly positive impact on survival of adjuvant chemotherapy comprising 6 months of gemcitabine or fluorouracil/folinic acid. Delayed adjuvant chemoradiation is considered as an option in cases of positive margins. Borderline resectable pancreatic cancer (BRPC) is defined as a tumour involving the mesenteric vasculature to a limited extend. Resection of these tumours is technically feasible, yet runs the high risk of a R1 resection. Neoadjuvant treatment probably offers the best chance of achieving successful R0 resection and long-term survival, but the best treatment options should be determined in prospective randomised studies. Gemcitabine has for 15 years been the only validated therapy for advanced PC. Following decades of negative phase III studies, increasing evidence now suggests that further significant improvements to overall survival can be achieved via either Folfirinox or gemcitabine + nab-paclitaxel regimens. Progress in systemic therapy may improve the chances of resection in borderline resectable pancreatic cancer (BRPC) or locally advanced PC. This requires first enhancing knowledge of the genetic events driving carcinogenesis, which may then be translated into clinical studies.

7 Review The role of the FOLFIRINOX regimen for advanced pancreatic cancer. 2013

Conroy, Thierry / Gavoille, Céline / Samalin, Emmanuelle / Ychou, Marc / Ducreux, Michel. ·EA 4360 and Department of Medical Oncology, Centre Alexis Vautrin, Université de Lorraine, Vandoeuvre-lès-Nancy, France. t.conroy@nancy.unicancer.fr ·Curr Oncol Rep · Pubmed #23341367.

ABSTRACT: In 2010, the FOLFIRINOX regimen (bolus and infusional 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) emerged as a new option in patients with metastatic pancreatic cancer and a good performance status. However, at that time, some doubts were raised regarding safety issues. Similarly, no data on FOLFIRINOX were published in patients with unresectable/locally advanced or borderline resectable pancreatic cancer. This article presents the available experience with FOLFIRINOX outside clinical trials in metastatic and locally advanced pancreatic cancer patients. The safety of the regimen in patients with biliary stents and in previously treated patients is also described. FOLFIRINOX usage in clinical practice, including modification of the regimen (omission of bolus 5-fluorouracil; FOLFOXIRI regimen), is also presented. These data suggest that a phase III randomized study is warranted to further explore the role of FOLFIRINOX in locally advanced pancreatic cancer.

8 Review [Chemotherapy of metastatic pancreatic adenocarcinoma: challenges and encouraging results]. 2011

Conroy, Thierry / Mitry, Emmanuel. ·Centre Alexis-Vautrin, département d'oncologie médicale, Vandœuvre-lès-Nancy, France. t.conroy@nancy.unicancer.fr ·Bull Cancer · Pubmed #22133915.

ABSTRACT: The outcome for patients with metastatic pancreatic ductal adenocarcinoma is dismal. In this article, we will review current first-line treatments for metastatic pancreatic adenocarcinoma focusing on phase III randomized studies. Single-agent gemcitabine, the reference treatment since 1995, offers only slight benefit. Numerous trials using gemcitabine in combination with different cytotoxic agents have resulted in no major improvement compared to gemcitabine alone. Only the gemcitabine-erlotinib combination has shown a small, but statistically improvement in survival. In selected patients with good performance status ECOG 0-1, no cardiac ischemia and almost normal bilirubin level, the Folfirinox regimen, when compared to gemcitabine as single agent, was associated with more toxicities, but also with significant increased survival and delay in the degradation of quality of life. So, Folfirinox is a new more toxic and more efficient regimen that may be considered in patients with good performance status.

9 Review Metastatic pancreatic cancer: old drugs, new paradigms. 2011

Conroy, Thierry / Gavoille, Céline / Adenis, Antoine. ·Department of Medical Oncology, Centre Alexis Vautrin, Nancy University, Vandoeuvre-lès-Nancy, France. t.conroy@nancy.fnclcc.fr ·Curr Opin Oncol · Pubmed #21505335.

ABSTRACT: PURPOSE OF REVIEW: Metastatic pancreatic ductal adenocarcinoma has a grim prognosis and gemcitabine has been the reference treatment for 15 years. In this article, we will review current first-line treatments for metastatic pancreatic adenocarcinoma focusing on randomized studies. RECENT FINDINGS: Among the numerous randomized phase III studies comparing gemcitabine as single agent to gemcitabine combined to a new agent, only the gemcitabine-erlotinib combination has shown a small, but statistical improvement in survival. A trend to better survival was also observed with a gemcitabine-capecitabine regimen. The use of low-weight heparin may be of value to reduce venous thromboembolic events. In selected patients with good performance status ECOG 0-1, the Folfirinox regimen, when compared with gemcitabine, was associated with more toxicities and significantly increased median survival from 6.8 to 11.1 months. SUMMARY: Gemcitabine (with or without erlotinib or capecitabine) is still the reference treatment in patients with ECOG performance status 2. Folfirinox is a new more toxic and more efficient regimen that may be considered in patients with good performance status.

10 Guideline Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. 2015

Ducreux, M / Cuhna, A Sa / Caramella, C / Hollebecque, A / Burtin, P / Goéré, D / Seufferlein, T / Haustermans, K / Van Laethem, J L / Conroy, T / Arnold, D / Anonymous6570840. ·Département de médecine, Gustave Roussy, Villejuif Faculté de Médecine, Université Paris Sud, le Kremlin Bicêtre. · Faculté de Médecine, Université Paris Sud, le Kremlin Bicêtre Département de Chirugie Hépato-biliaire, Hopital Paul Brousse, Villejuif. · Département d'imagerie. · Département de médecine, Gustave Roussy, Villejuif Département d'Innovation Thérapeutique. · Département de médecine, Gustave Roussy, Villejuif. · Département de Chirurgie Générale, Gustave Roussy, Villejuif, France. · Department of Internal Medicine I, Ulm University Hospital Medical Center, Ulm, Germany. · Department of Radiation Oncology, Leuven Kankerinstitute, Leuven. · Departement of Gastroenterology, Hôpital Erasme, Cliniques Universitaires de Bruxelles, Brussels, Belgium. · Département de médecine, Institut de Cancérologie de Lorraine, Vandoeuvre lés Nancy, France. · Department of Medical Oncology, Tumor Biology Center, Freiburg, Germany. ·Ann Oncol · Pubmed #26314780.

ABSTRACT: -- No abstract --

11 Clinical Trial FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. 2018

Conroy, Thierry / Hammel, Pascal / Hebbar, Mohamed / Ben Abdelghani, Meher / Wei, Alice C / Raoul, Jean-Luc / Choné, Laurence / Francois, Eric / Artru, Pascal / Biagi, James J / Lecomte, Thierry / Assenat, Eric / Faroux, Roger / Ychou, Marc / Volet, Julien / Sauvanet, Alain / Breysacher, Gilles / Di Fiore, Frédéric / Cripps, Christine / Kavan, Petr / Texereau, Patrick / Bouhier-Leporrier, Karine / Khemissa-Akouz, Faiza / Legoux, Jean-Louis / Juzyna, Béata / Gourgou, Sophie / O'Callaghan, Christopher J / Jouffroy-Zeller, Claire / Rat, Patrick / Malka, David / Castan, Florence / Bachet, Jean-Baptiste / Anonymous3361096. ·From the Institut de Cancérologie de Lorraine and Université de Lorraine (T.C.) and Centre Hospitalier Universitaire (L.C.), Nancy, Hôpital Beaujon and University Paris VII, Clichy (P.H., A.S.), Hôpital Huriez, Lille (M.H.), Centre Paul Strauss, Strasbourg (M.B.A.), Institut Paoli-Calmettes, Marseille (J.-L.R.), Centre Antoine-Lacassagne, Nice (E.F.), Hôpital Jean-Mermoz, Lyon (P.A.), Hôpital Trousseau, Tours (T.L.), Centre Hospitalier Universitaire de Saint-Eloi (E.A.) and Institut du Cancer de Montpellier-Val d'Aurelle, Université de Montpellier (M.Y., S.G., F.C.), Montpellier, Centre Hospitalier Départemental Vendée, La Roche-sur-Yon (R.F.), Centre Hospitalier Universitaire Robert Debré, Reims (J.V.), Hôpital Louis Pasteur, Colmar (G.B.), Normandie University, Rouen University Hospital, Rouen (F.D.F.), Hôpital Layné, Mont-de-Marsan (P.T.), Centre Hospitalier Universitaire Côte de Nacre, Caen (K.B.-L.), Hôpital Saint-Jean, Perpignan (F.K.-A.), Centre Hospitalier Régional, Orléans (J.-L.L.), R&D Unicancer (B.J., C.J.-Z.) and Sorbonne Université, Hôpitaux Universitaires Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris (J.-B.B.), Paris, Gustave Roussy, Université Paris-Saclay, Villejuif (D.M.), and Centre Hospitalier Universitaire, Dijon (P.R.) - all in France · and the Princess Margaret Cancer Centre, Toronto (A.C.W.), Kingston General Hospital (J.J.B.) and the Canadian Cancer Trials Group, Queen's University (C.J.O.), Kingston, ON, the Ottawa Health Research Institute, Ottawa (C.C.), and Segal Cancer Centre, Jewish General Hospital, Montreal (P.K.) - all in Canada. ·N Engl J Med · Pubmed #30575490.

ABSTRACT: BACKGROUND: Among patients with metastatic pancreatic cancer, combination chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) leads to longer overall survival than gemcitabine therapy. We compared the efficacy and safety of a modified FOLFIRINOX regimen with gemcitabine as adjuvant therapy in patients with resected pancreatic cancer. METHODS: We randomly assigned 493 patients with resected pancreatic ductal adenocarcinoma to receive a modified FOLFIRINOX regimen (oxaliplatin [85 mg per square meter of body-surface area], irinotecan [180 mg per square meter, reduced to 150 mg per square meter after a protocol-specified safety analysis], leucovorin [400 mg per square meter], and fluorouracil [2400 mg per square meter] every 2 weeks) or gemcitabine (1000 mg per square meter on days 1, 8, and 15 every 4 weeks) for 24 weeks. The primary end point was disease-free survival. Secondary end points included overall survival and safety. RESULTS: At a median follow-up of 33.6 months, the median disease-free survival was 21.6 months in the modified-FOLFIRINOX group and 12.8 months in the gemcitabine group (stratified hazard ratio for cancer-related event, second cancer, or death, 0.58; 95% confidence interval [CI], 0.46 to 0.73; P<0.001). The disease-free survival rate at 3 years was 39.7% in the modified-FOLFIRINOX group and 21.4% in the gemcitabine group. The median overall survival was 54.4 months in the modified-FOLFIRINOX group and 35.0 months in the gemcitabine group (stratified hazard ratio for death, 0.64; 95% CI, 0.48 to 0.86; P=0.003). The overall survival rate at 3 years was 63.4% in the modified-FOLFIRINOX group and 48.6% in the gemcitabine group. Adverse events of grade 3 or 4 occurred in 75.9% of the patients in the modified-FOLFIRINOX group and in 52.9% of those in the gemcitabine group. One patient in the gemcitabine group died from toxic effects (interstitial pneumonitis). CONCLUSIONS: Adjuvant therapy with a modified FOLFIRINOX regimen led to significantly longer survival than gemcitabine among patients with resected pancreatic cancer, at the expense of a higher incidence of toxic effects. (Funded by R&D Unicancer and others; ClinicalTrials.gov number, NCT01526135 ; EudraCT number, 2011-002026-52 .).

12 Clinical Trial Retrospective Analysis of CA19-9 Decrease in Patients with Metastatic Pancreatic Carcinoma Treated with FOLFIRINOX or Gemcitabine in a Randomized Phase III Study (ACCORD11/PRODIGE4). 2017

Robert, Marie / Jarlier, Marta / Gourgou, Sophie / Desseigne, Françoise / Ychou, Marc / Bouché, Olivier / Juzyna, Beata / Conroy, Thierry / Bennouna, Jaafar. ·Department of Medical Oncology, Institut de Cancérologie de l'Ouest, St. Herblain, France. ·Oncology · Pubmed #28982109.

ABSTRACT: OBJECTIVES: Carbohydrate antigen 19-9 (CA19-9) is a sensitive and specific serum marker in pancreatic cancer. Our retrospective analysis aims to evaluate CA19-9 decrease in patients with metastatic pancreatic cancer treated in ACCORD11/PRODIGE4 (FOLFIRINOX vs. gemcitabine). METHODS: A total of 342 patients were treated. CA19-9 was measured at 8 weeks (±2) in 160 patients from a total of 282 with abnormal CA19-9 values at baseline (gemcitabine arm, n = 75; FOLFIRINOX arm, n = 85). In the present study, 8-week CA19-9 decrease or greater CA19-9 decrease according to the 20 and 90% thresholds were analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated in each subgroup. RESULTS: In the FOLFIRINOX arm, patients with an 8-week CA19-9 decrease or greater CA19-9 decrease ≥20% showed improved median OS, PFS, and objective response rate. In the overall study population, median OS and PFS were significantly improved in patients with an 8-week CA19-9 decrease ≥20% (vs. <20%). The 8-week CA19-9 decrease was predictive of PFS (interaction test significant according to treatment arm; p = 0.006). CONCLUSION: An 8-week CA19-9 decrease ≥20% is a prognostic factor for OS and PFS. The 8-week CA19-9 decrease (20% threshold) is predictive of PFS. It could help to evaluate the efficacy of FOLFIRINOX and gemcitabine regimens.

13 Clinical Trial Response to FOLFIRINOX by gender in patients with metastatic pancreatic cancer: Results from the PRODIGE 4/ ACCORD 11 randomized trial. 2017

Lambert, Aurélien / Jarlier, Marta / Gourgou Bourgade, Sophie / Conroy, Thierry. ·Department of medical oncology, Institut de Cancérologie de Lorraine, Vandoeuvre-lès-Nancy, France. · Biostatistics unit, Institut régional du cancer de Montpellier, Parc Euromédecine, Montpellier, France. ·PLoS One · Pubmed #28931010.

ABSTRACT: BACKGROUND: Hohla et al. suggested that female gender could positively predict response to FOLFIRINOX in patients with advanced pancreatic cancer. In this study, we explored the response to the FOLFIRINOX regimen by gender within the trial PRODIGE4/ACCORD 11. PATIENTS AND METHODS: Data were described by gender, both in FOLFIRINOX group and in the intention-to-treat population of the trial. The relative effect of gender (females in comparison to males) on overall survival (OS) and progression-free survival was estimated by using a Cox proportional hazard model and was presented with the Hazard Ratio and their 95% confidence interval. The analysis of prognostic factors of OS included also: age (older than 65 years), ECOG performance status, primary tumor location, synchronous metastases, number of metastatic sites, hepatic metastasis, pulmonary metastases, lymph node metastases, level of Albumin and level of serum carbohydrate antigen 19-9 and three domains from the EORTC Quality of Life QLQC-30 questionnaire. RESULTS: The FOLFIRINOX group (N = 171 patients) included 106 women (62%) and 65 men. No significant differences were observed between genders regarding demographic and clinical parameters, excepted for lymph nodes metastasis (17% and 35% in women and men respectively; p = 0.012). Median OS was longer for females as compared to males in FOLFIRINOX group (13.1 versus 10.3 months respectively; HR = 0.73; 95% CI, 0.51-1.06). Similarly, median PFS was superior (7.2 versus 5.9 months; HR = 0.79; 95% CI, 0.57-1.10). Nevertheless, in both cases, the differences were not statistically significant (p = 0.10 et p = 0.169, respectively). CONCLUSIONS: In this study, the overall survival and progression-free survival rates were not significantly higher for females than for males in FOLFIRINOX group (HR = 0.73; 95% CI, 0.51-1.06 and HR = 0.79; 95% CI, 0.57-1.10 respectively). Even if the percentage of patients with lymph node metastasis is higher for males than for females, the interaction between gender and lymph node metastasis was non-significant. Our exploratory analysis did not permit to definitively conclude about a possible effect of gender on the prognosis of patients under FOLFIRINOX. This subject deserves further evaluation. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT00112658. KEY MESSAGE: Our analysis suggests that FOLFIRINOX, as first-line option for patients with metastatic pancreatic cancer who are younger than 76 years and who have a good performance status (ECOG 0 or 1), no cardiac ischemia and normal or nearly normal bilirubin levels, is beneficial, but not particularly in female patients.

14 Clinical Trial Radiation plus docetaxel and cisplatin in locally advanced pancreatic carcinoma: a non-comparative randomized phase II trial. 2014

Ducreux, Michel / Giovannini, Marc / Baey, Charlotte / Llacer, Carmen / Bennouna, Jaafar / Adenis, Antoine / Peiffert, Didier / Mornex, Françoise / Abbas, Moncef / Boige, Valèrie / Pignon, Jean-Pierre / Conroy, Thierry / Cellier, Patrice / Juzyna, Beata / Viret, Frédéric. ·Gustave Roussy, Villejuif, France; Université Paris Sud, Le Kremlin Bicetre, France. Electronic address: michel.ducreux@gustaveroussy.fr. · Institut Paoli Calmettes, Marseille, France. · Gustave Roussy, Villejuif, France. · Institut du Cancer Montpellier - Val d'Aurelle, Montpellier, France. · Institut de Cancérologie de l'Ouest - René Gauducheau, Nantes, France. · Centre Oscar Lambret, Lille, France. · Institut de Cancérologie de Lorraine - Alexis Vautrin, Nancy, France. · Hôpital Lyon Sud, Lyon, France. · Institut de Cancérologie de l'Ouest - Paul Papin, Angers, France. · Unicancer, Paris, France. ·Dig Liver Dis · Pubmed #25027552.

ABSTRACT: BACKGROUND: We performed a randomized, non-comparative phase II study evaluating docetaxel in combination with either daily continuous (protracted IV) 5-fluorouracil or cisplatin administered weekly, concurrent to radiotherapy in the treatment of locally advanced pancreatic carcinoma. Results of the docetaxel plus cisplatin regimen are reported. METHODS: Forty chemotherapy-naive patients with locally advanced pancreatic carcinoma were randomly assigned to receive 5-fluorouracil and docetaxel or docetaxel 20mg/m(2) and cisplatin 20mg/m(2)/week, plus concurrent radiotherapy for 6 weeks. The radiation dose to the primary tumour was 54Gy in 30 fractions. The trial's primary endpoint was the 6-month crude non-progression rate. RESULTS: 51 patients from 7 centres were included in the docetaxel-cisplatin treatment group. Six-month non-progression rate was 39% (95% confidence interval: 26-53). Median overall survival was 9.6 months (95% confidence interval: 2.4-60.7); 6 complete and 8 partial responses were obtained. Six patients survived more than 2 years after their inclusion in the trial. Grade ≥3 toxicity was reported in 63% of patients; no treatment-related death occurred. Severe toxicities were mainly anorexia (22%), vomiting (20%) and fatigue (24%). CONCLUSIONS: Despite inadequate efficacy according to the main end point, this regimen gave a satisfactory rate of objective response (27%) with tolerable toxicity.

15 Clinical Trial Impact of FOLFIRINOX compared with gemcitabine on quality of life in patients with metastatic pancreatic cancer: results from the PRODIGE 4/ACCORD 11 randomized trial. 2013

Gourgou-Bourgade, Sophie / Bascoul-Mollevi, Caroline / Desseigne, Françoise / Ychou, Marc / Bouché, Olivier / Guimbaud, Rosine / Bécouarn, Yves / Adenis, Antoine / Raoul, Jean-Luc / Boige, Valérie / Bérille, Jocelyne / Conroy, Thierry. ·Centre Léon Bérard, Lyon, France. ·J Clin Oncol · Pubmed #23213101.

ABSTRACT: PURPOSE: To compare the quality of life (QoL) of patients receiving oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) or gemcitabine as first-line chemotherapy and to assess whether pretreatment QoL predicts survival in patients with metastatic pancreatic cancer. PATIENTS AND METHODS: Three hundred forty-two patients with performance status 0 or 1 were randomly assigned to receive FOLFIRINOX (oxaliplatin, 85 mg/m(2); irinotecan, 180 mg/m(2); leucovorin, 400 mg/m(2); and fluorouracil, 400 mg/m(2) bolus followed by 2,400 mg/m(2) 46-hour continuous infusion, once every 2 weeks) or gemcitabine 1,000 mg/m(2) weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. QoL was assessed using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire C30 every 2 weeks. RESULTS: Improvement in global health status (GHS; P < .001) was observed in the FOLFIRINOX arm and improvement in emotional functioning (P < .001) was observed in both arms, along with a decrease in pain, insomnia, anorexia, and constipation in both arms. A significant increase in diarrhea was observed in the FOLFIRINOX arm during the first 2 months of chemotherapy. Time until definitive deterioration ≥ 20 points was significantly longer for FOLFIRINOX compared with gemcitabine for GHS, physical, role, cognitive, and social functioning, and six symptom domains (fatigue, nausea/vomiting, pain, dyspnea, anorexia, and constipation). Physical functioning, constipation, and dyspnea were independent significant prognostic factors for survival with treatment arm, age older than 65 years, and low serum albumin. CONCLUSION: FOLFIRINOX significantly reduces QoL impairment compared with gemcitabine in patients with metastatic pancreatic cancer. Furthermore, baseline QoL scores improved estimation of survival probability when added to baseline clinical and demographic variables.

16 Clinical Trial FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. 2011

Conroy, Thierry / Desseigne, Françoise / Ychou, Marc / Bouché, Olivier / Guimbaud, Rosine / Bécouarn, Yves / Adenis, Antoine / Raoul, Jean-Luc / Gourgou-Bourgade, Sophie / de la Fouchardière, Christelle / Bennouna, Jaafar / Bachet, Jean-Baptiste / Khemissa-Akouz, Faiza / Péré-Vergé, Denis / Delbaldo, Catherine / Assenat, Eric / Chauffert, Bruno / Michel, Pierre / Montoto-Grillot, Christine / Ducreux, Michel / Anonymous1530694 / Anonymous1540694. ·Nancy University and Department of Medical Oncology, Centre Alexis Vautrin, Nancy, France. t.conroy@nancy.fnclcc.fr ·N Engl J Med · Pubmed #21561347.

ABSTRACT: BACKGROUND: Data are lacking on the efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) as compared with gemcitabine as first-line therapy in patients with metastatic pancreatic cancer. METHODS: We randomly assigned 342 patients with an Eastern Cooperative Oncology Group performance status score of 0 or 1 (on a scale of 0 to 5, with higher scores indicating a greater severity of illness) to receive FOLFIRINOX (oxaliplatin, 85 mg per square meter of body-surface area; irinotecan, 180 mg per square meter; leucovorin, 400 mg per square meter; and fluorouracil, 400 mg per square meter given as a bolus followed by 2400 mg per square meter given as a 46-hour continuous infusion, every 2 weeks) or gemcitabine at a dose of 1000 mg per square meter weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. Six months of chemotherapy were recommended in both groups in patients who had a response. The primary end point was overall survival. RESULTS: The median overall survival was 11.1 months in the FOLFIRINOX group as compared with 6.8 months in the gemcitabine group (hazard ratio for death, 0.57; 95% confidence interval [CI], 0.45 to 0.73; P<0.001). Median progression-free survival was 6.4 months in the FOLFIRINOX group and 3.3 months in the gemcitabine group (hazard ratio for disease progression, 0.47; 95% CI, 0.37 to 0.59; P<0.001). The objective response rate was 31.6% in the FOLFIRINOX group versus 9.4% in the gemcitabine group (P<0.001). More adverse events were noted in the FOLFIRINOX group; 5.4% of patients in this group had febrile neutropenia. At 6 months, 31% of the patients in the FOLFIRINOX group had a definitive degradation of the quality of life versus 66% in the gemcitabine group (hazard ratio, 0.47; 95% CI, 0.30 to 0.70; P<0.001). CONCLUSIONS: As compared with gemcitabine, FOLFIRINOX was associated with a survival advantage and had increased toxicity. FOLFIRINOX is an option for the treatment of patients with metastatic pancreatic cancer and good performance status. (Funded by the French government and others; ClinicalTrials.gov number, NCT00112658.).

17 Article Chemotherapy for pancreatic cancer: the rise of multidrug regimens. 2018

Malka, David / Borbath, Ivan / Conroy, Thierry. ·Gustave Roussy, Université Paris-Saclay, Département de Médecine Oncologique, Villejuif, France. Electronic address: david.malka@gustaveroussy.fr. · Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Service d'Hépato-Gastroentérologie, Brussels, Belgium. · Institut de Cancérologie de Lorraine and Université de Lorraine, Nancy, France. ·Lancet Gastroenterol Hepatol · Pubmed #30215353.

ABSTRACT: -- No abstract --

18 Article An assessment of the benefit-risk balance of FOLFIRINOX in metastatic pancreatic adenocarcinoma. 2016

Péron, Julien / Roy, Pascal / Conroy, Thierry / Desseigne, Françoise / Ychou, Marc / Gourgou-Bourgade, Sophie / Stanbury, Trevor / Roche, Laurent / Ozenne, Brice / Buyse, Marc. ·CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Service de Biostatistiques, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, 69495 Pierre-Bénite, France. · Medical Oncology Department, Centre Hospitalier Lyon-Sud, Institut de Cancérologie des Hospices Civils de Lyon-IC-HCL, 69495 Pierre-Bénite, France. · Institut de Cancérologie de Lorraine, Alexis Vautrin Center, 54500 Vandœuvre-lès-Nancy, France. · Medical Oncology Department, Centre Léon Bérard, 69373 Lyon, France. · Institut Régional du Cancer Montpellier, Val d'Aurelle, 34298 Montpellier, France. · R&D UNICANCER, 75013 Paris, France. · International Drug Development Institute (IDDI), San Francisco, CA 94109, USA. ·Oncotarget · Pubmed #27765912.

ABSTRACT: BACKGROUND: We sought to assess the benefit-risk balance of FOLFIRINOX versus gemcitabine in patients with metastatic pancreatic adenocarcinoma. METHODS: We used generalized pairwise comparisons. This statistical method permits the simultaneous analysis of several prioritized outcome measures. The first priority outcome was survival time (OS). Differences in OS that exceeded two months were considered clinically relevant. The second priority outcome was toxicity. The overall treatment effect was quantified using the net chance of a better outcome, which can be interpreted as the net probability for a random patient treated in the FOLFIRINOX group to have a better overall outcome than a random patient in the gemcitabine group. RESULTS: In this trial 342 patients received either FOLFIRINOX or gemcitabine. The net chance of a better outcome favored strongly and significantly the FOLFIRINOX group (24.7; P<.001), suggesting a favorable benefit-risk balance of FOLFIRINOX versus gemcitabine. The positive benefit-risk balance of FOLFIRINOX was observed throughout all sensitivity analyses. CONCLUSIONS: Generalized pairwise comparisons are useful to perform a quantitative assessment of the benefit-risk balance of new treatments. It provides a clinically intuitive way of comparing patients with respect to all important efficacy and toxicity outcomes. Overall the benefit-risk balance of FOLFIRINOX was strongly positive.

19 Article Applying the Longitudinal Model from Item Response Theory to Assess Health-Related Quality of Life in the PRODIGE 4/ACCORD 11 Randomized Trial. 2016

Barbieri, Antoine / Anota, Amélie / Conroy, Thierry / Gourgou-Bourgade, Sophie / Juzyna, Beata / Bonnetain, Franck / Lavergne, Christian / Bascoul-Mollevi, Caroline. ·Biometrics Unit-CTD INCa, Institut régional du Cancer Montpellier (ICM) - Val d'Aurelle, Montpellier, France (AB, SG-B, CB-M) · Institut Montpelliérain Alexander Grothendieck, University of Montpellier, Montpellier, France (AB, CL) · National Quality of Life in Oncology Platform, France (AA, TC, FB) · Methodological and Quality of Life Unit in Oncology (EA 3181), Besançon, France (AA, FB) · Institut de Cancérologie de Lorraine, Nancy, France (TC) · Unicancer R&D, Paris, France (BJ) · Université Paul-Valéry Montpellier 3, Montpellier, France (CL) ·Med Decis Making · Pubmed #26683246.

ABSTRACT: INTRODUCTION: A new longitudinal statistical approach was compared to the classical methods currently used to analyze health-related quality-of-life (HRQoL) data. The comparison was made using data in patients with metastatic pancreatic cancer. METHODS: Three hundred forty-two patients from the PRODIGE4/ACCORD 11 study were randomly assigned to FOLFIRINOX versus gemcitabine regimens. HRQoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30. The classical analysis uses a linear mixed model (LMM), considering an HRQoL score as a good representation of the true value of the HRQoL, following EORTC recommendations. In contrast, built on the item response theory (IRT), our approach considered HRQoL as a latent variable directly estimated from the raw data. For polytomous items, we extended the partial credit model to a longitudinal analysis (longitudinal partial credit model [LPCM]), thereby modeling the latent trait as a function of time and other covariates. RESULTS: Both models gave the same conclusions on 11 of 15 HRQoL dimensions. HRQoL evolution was similar between the 2 treatment arms, except for the symptoms of pain. Indeed, regarding the LPCM, pain perception was significantly less important in the FOLFIRINOX arm than in the gemcitabine arm. For most of the scales, HRQoL changes over time, and no difference was found between treatments in terms of HRQoL. DISCUSSION: The use of LMM to study the HRQoL score does not seem appropriate. It is an easy-to-use model, but the basic statistical assumptions do not check. Our IRT model may be more complex but shows the same qualities and gives similar results. It has the additional advantage of being more precise and suitable because of its direct use of raw data.

20 Minor FOLFIRINOX Adjuvant Therapy for Pancreatic Cancer. Reply. 2019

Malka, David / Castan, Florence / Conroy, Thierry. ·Gustave Roussy, Villejuif, France. · Institut de Cancérologie de Montpellier, Montpellier, France. · Institut de Cancérologie de Lorraine, Vandoeuvre-lès-Nancy, France t.conroy@nancy.unicancer.fr. ·N Engl J Med · Pubmed #30893544.

ABSTRACT: -- No abstract --