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Pancreatic Neoplasms: HELP
Articles by Benoist Chibaudel
Based on 9 articles published since 2009
(Why 9 articles?)
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Between 2009 and 2019, B. Chibaudel wrote the following 9 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 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.

2 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 / Anonymous2561138 / Anonymous2571138 / Anonymous2581138 / Anonymous2591138 / Anonymous2601138 / Anonymous2611138 / Anonymous2621138 / Anonymous2631138 / Anonymous2641138 / Anonymous2651138. ·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.

3 Clinical Trial Nab-paclitaxel plus either gemcitabine or simplified leucovorin and fluorouracil as first-line therapy for metastatic pancreatic adenocarcinoma (AFUGEM GERCOR): a non-comparative, multicentre, open-label, randomised phase 2 trial. 2017

Bachet, Jean-Baptiste / Hammel, Pascal / Desramé, Jérôme / Meurisse, Aurélia / Chibaudel, Benoist / André, Thierry / Debourdeau, Philippe / Dauba, Jérome / Lecomte, Thierry / Seitz, Jean-François / Tournigand, Christophe / Aparicio, Thomas / Meyer, Véronique Guerin / Taieb, Julien / Volet, Julien / Monier, Amandine / Bonnetain, Franck / Louvet, Christophe. ·Sorbonne Universités, UPMC Univ Paris 06, Paris, France; Department of Hepato-Gastroenterology, Groupe hospitalier Pitié Salpêtrière, Paris, France. Electronic address: jean-baptiste.bachet@aphp.fr. · Department of Digestive Oncology, Hôpital Beaujon, Paris, France. · Department of Hepato-Gastroenterology, Hôpital Privé Jean Mermoz, Lyon, France. · Department of Methodology and Quality of Life in Oncology, INSERM UMR 1098, Hôpital Universitaire de Besancon, Paris, France. · Department of Oncology, Institut Franco-Britannique, Levallois-Perret, Paris, France. · Department of Oncology, Hôpital Saint Antoine, Paris, France. · Department of Oncology, Institut Saint Catherine, Avignon, France. · Department of Oncology, Hôpital Layne Mont de Marsan, Mont de Marsan, France. · Department of Hepato-Gastroenterology, Hôpital Trousseau, Tours, France. · CHU La Timone, Marseille, France. · Department of Oncology, CHU Henri Mondor, Créteil, France. · Department of Hepato-Gastroenterology, CHU Avicenne, Bobigny, France. · Department of Oncology, Institut de cancérologie de L'Ouest Paul Papin, Angers, France. · Department of Gastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, Paris, France. · Department of Hepato-Gastroenterology, CHU Robert Debré, Reims, France. · GERCOR (Groupe Coopérateur Multidisciplinaire en Oncologie), Paris, France. · Department of Oncology, Institut Mutualiste Montsouris, Paris, France. ·Lancet Gastroenterol Hepatol · Pubmed #28397697.

ABSTRACT: BACKGROUND: Nab-paclitaxel plus gemcitabine has become a standard treatment regimen in patients with metastatic pancreatic adenocarcinoma; however, retrospective data suggest that gemcitabine might be inefficient in 50-60% of patients and thus not an optimum regimen in combination with nab-paclitaxel. We did a phase 2 trial to assess the activity and safety of a new regimen of nab-paclitaxel plus simplified leucovorin and fluorouracil. METHODS: We did a non-comparative, multicentre, open-label, randomised phase 2 trial in 15 hospitals and institutions in France. Eligible participants were previously untreated patients with metastatic pancreatic adenocarcinoma (previous adjuvant chemotherapy after curative intent resection was allowed if the interval between the end of chemotherapy and relapse was more than 12 months). Patients had to have at least one measurable lesion assessed by CT scan or MRI and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. We randomly assigned participants (1:2) centrally to 28-day cycles of either gemcitabine plus nab-paclitaxel or simplified leucovorin and fluorouracil plus nab-paclitaxel. The randomisation was by minimisation, stratified by centre and ECOG performance status. Drugs were administered in each cycle as follows: nab-paclitaxel (125 mg/m FINDINGS: Between Dec 12, 2013, and Oct 31, 2014, we randomly assigned 114 patients to treatment: 75 patients to the leucovorin and fluorouracil group and 39 to the gemcitabine group. One patient in the leucovorin and fluorouracil group did not have a 4-month assessment, and was thus excluded from the modified ITT analysis. Median follow-up was 13·1 months (95% CI 12·5-14·1). At 4 months, 40 (56%, 90% CI 45-66) of 72 patients in the leucovorin and fluorouracil group were alive and free from disease progression (21 [54%, 40-68] of 39 patients in the gemcitabine group were also alive and progression-free at 4 months). Grade 3-4 adverse events occurred in 33 (87%) of 38 patients in the gemcitabine group and in 56 (77%) of 73 patients in the leucovorin and fluorouracil group, with different toxicity profiles. The most common grade 3-4 adverse events in the leucovorin and fluorouracil group were neutropenia without fever (17 [23%]), fatigue (16 [22%]), paraesthesia (14 [19%]), diarrhoea (nine [12%]), and mucositis (seven [10%]); in the gemcitabine group they were neutropenia without fever (12 [32%]), thrombocytopenia (seven [18%]), fatigue (eight [21%]), anaemia (five [13%]), increased alanine aminotransferase and aspartate aminotransferase concentrations (five [13%] for both), and paraesthesia (four [11%]). Two participants died; one in the leucovorin and fluorouracil group from septic shock, and one in the gemcitabine group from diabetes compensation with acidosis; these deaths were deemed to be not related to treatment. Treatment-related serious adverse events occurred in 28 (38%) of 73 patients in the leucovorin and fluorouracil group and in 14 (37%) of 38 in the gemcitabine group. INTERPRETATION: Nab-paclitaxel plus simplified leucovorin and fluorouracil fulfilled the primary endpoint in that more than the required 50% of our study population were progression-free at 4 months, with a tolerable toxicity profile. This regimen thus deserves further assessment in a phase 3 trial. FUNDING: GERCOR (Groupe Coopérateur Multidisciplinaire en Oncologie) and Celgene through grants to GERCOR.

4 Clinical Trial Prognostic nomogram and score to predict overall survival in locally advanced untreated pancreatic cancer (PROLAP). 2016

Vernerey, Dewi / Huguet, Florence / Vienot, Angélique / Goldstein, David / Paget-Bailly, Sophie / Van Laethem, Jean-Luc / Glimelius, Bengt / Artru, Pascal / Moore, Malcolm J / André, Thierry / Mineur, Laurent / Chibaudel, Benoist / Benetkiewicz, Magdalena / Louvet, Christophe / Hammel, Pascal / Bonnetain, Franck. ·Methodological and Quality of Life in Oncology Unit, EA 3181, University Hospital of Besançon, 3 Boulevard Alexandre Fleming, Besançon 25030, France. · Oncology Multidisciplinary Research Group (GERCOR), 151 rue du Faubourg Saint Antoine, Paris 75011, France. · Department of Radiotherapy, Tenon Hospital (AP-HP), 4 rue de la Chine, Paris 75020, France. · Department of Gastroenterology, University Hospital of Besançon, 3 Boulevard Alexandre Fleming, Besançon 25030, France. · Department of Medical Oncology, Prince of Wales hospital and Prince of Wales Clinical school, UNSW, Sydney, New South Wales 2031, Australia. · AGITG (Australasian Gastrointestinal Trials Group), 119-143 Missenden Rd, Camperdown, New South Wales 2050, Australia. · Department of Gastroenterology, Erasme University Hospital, Route de Lennik 808, Brussels 1070, Belgium. · Department of Radiology, Oncology and Radiation Science, University of Uppsala, Uppsala 75105, Sweden. · Department of Gastroenterology, Jean Mermoz Hospital, 55 avenue Mermoz, Lyon 69008, France. · Department of Medical Oncology, Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada. · Department of Medical Oncology, Saint-Antoine Hospital (AP-HP), 184 rue du Faubourg Saint Antoine, Paris 75011, France. · Department of Radiotherapy and Medical Oncology, Sainte-Catherine Institute, 250 Chemin de Baigne Pieds, Avignon 84918, France. · Department of Medical Oncology, Franco-British Hospital Institute, 3 Rue Barbès, Levallois-Perret 92300, France. · Department of Medical Oncology, Institute Mutualiste Montsouris, 42 Boulevard Jourdan, Paris 75014, France. · Department of Digestive Oncology, Beaujon Hospital (AP-HP), 100 boulevard du General Leclerc, Clichy 92110, France. ·Br J Cancer · Pubmed #27404456.

ABSTRACT: BACKGROUND: The management of locally advanced pancreatic cancer (LAPC) patients remains controversial. Better discrimination for overall survival (OS) at diagnosis is needed. We address this issue by developing and validating a prognostic nomogram and a score for OS in LAPC (PROLAP). METHODS: Analyses were derived from 442 LAPC patients enrolled in the LAP07 trial. The prognostic ability of 30 baseline parameters was evaluated using univariate and multivariate Cox regression analyses. Performance assessment and internal validation of the final model were done with Harrell's C-index, calibration plot and bootstrap sample procedures. On the basis of the final model, a prognostic nomogram and a score were developed, and externally validated in 106 consecutive LAPC patients treated in Besançon Hospital, France. RESULTS: Age, pain, tumour size, albumin and CA 19-9 were independent prognostic factors for OS. The final model had good calibration, acceptable discrimination (C-index=0.60) and robust internal validity. The PROLAP score has the potential to delineate three different prognosis groups with median OS of 15.4, 11.7 and 8.5 months (log-rank P<0.0001). The score ability to discriminate OS was externally confirmed in 63 (59%) patients with complete clinical data derived from a data set of 106 consecutive LAPC patients; median OS of 18.3, 14.1 and 7.6 months for the three groups (log-rank P<0.0001). CONCLUSIONS: The PROLAP nomogram and score can accurately predict OS before initiation of induction chemotherapy in LAPC-untreated patients. They may help to optimise clinical trials design and might offer the opportunity to define risk-adapted strategies for LAPC management in the future.

5 Clinical Trial Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients With Locally Advanced Pancreatic Cancer Controlled After 4 Months of Gemcitabine With or Without Erlotinib: The LAP07 Randomized Clinical Trial. 2016

Hammel, Pascal / Huguet, Florence / van Laethem, Jean-Luc / Goldstein, David / Glimelius, Bengt / Artru, Pascal / Borbath, Ivan / Bouché, Olivier / Shannon, Jenny / André, Thierry / Mineur, Laurent / Chibaudel, Benoist / Bonnetain, Franck / Louvet, Christophe / Anonymous6180866. ·Department of Digestive Oncology, Beaujon Hospital (AP-HP), Clichy, France. · Department of Radiotherapy, Tenon Hospital (AP-HP), Paris, France. · Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium. · Department of Medical Oncology, Prince of Wales Hospital, Sydney, Australia5Australasian Gastrointestinal Trials Group (AGITG), Camperdown, Australia6Prince of Wales Clinical School, University of New South Wales, Sydney, Australia. · Department of Radiology, Oncology, and Radiation Science, University of Uppsala, Uppsala, Sweden. · Department of Gastroenterology, Jean Mermoz Hospital, Lyon, France. · Department of Gastroenterology, Saint-Luc University Clinics, Brussels, Belgium. · Department of Gastroenterology, Robert Debré Hospital, Reims, France. · Australasian Gastrointestinal Trials Group (AGITG), Camperdown, Australia6Prince of Wales Clinical School, University of New South Wales, Sydney, Australia11Department of Medical Oncology, Nepean Hospital NSW, Sydney, Australia. · Department of Medical Oncology, Saint-Antoine Hospital (AP-HP), Paris, France. · Department of Radiotherapy and Medical Oncology, Sainte-Catherine Institute, Avignon, France. · Department of Medical Oncology, Franco-British Hospital Institute, Levallois-Perret, France15Oncology Multidisciplinary Research Group (GERCOR), Paris, France. · Department of Methodology and Quality of Life in Oncology, Hospital Minjoz, Besançon, France. · Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France. ·JAMA · Pubmed #27139057.

ABSTRACT: IMPORTANCE: In locally advanced pancreatic cancer, the role of chemoradiotherapy is controversial and the efficacy of erlotinib is unknown. OBJECTIVES: To assess whether chemoradiotherapy improves overall survival of patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine-based induction chemotherapy and to assess the effect of erlotinib on survival. DESIGN, SETTING, AND PARTICIPANTS: In LAP07, an international, open-label, phase 3 randomized trial, 449 patients were enrolled between 2008 and 2011. Follow-up ended in February 2013. INTERVENTIONS: In the first randomization, 223 patients received 1000 mg/m2 weekly of gemcitabine alone and 219 patients received 1000 mg/m2 of gemcitabine plus 100 mg/d of erlotinib. In the second randomization involving patients with progression-free disease after 4 months, 136 patients received 2 months of the same chemotherapy and 133 underwent chemoradiotherapy (54 Gy plus capecitabine). MAIN OUTCOMES AND MEASURES: The primary outcome was overall survival from the date of the first randomization. Secondary outcomes were the effect of erlotinib and quality assurance of radiotherapy on overall survival, progression-free survival of gemcitabine-erlotinib and erlotinib maintenance with gemcitabine alone at the second randomization, and toxic effects. RESULTS: A total of 442 of the 449 patients (232 men; median age, 63.3 years) enrolled underwent the first randomization. Of these, 269 underwent the second randomization. Interim analysis was performed when 221 patients died (109 in the chemoradiotherapy group and 112 in the chemotherapy group), reaching the early stopping boundaries for futility. With a median follow-up of 36.7 months, the median overall survival from the date of the first randomization was not significantly different between chemotherapy at 16.5 months (95% CI, 14.5-18.5 months) and chemoradiotherapy at 15.2 months (95% CI, 13.9-17.3 months; hazard ratio [HR], 1.03; 95% CI, 0.79-1.34; P = .83). Median overall survival from the date of the first randomization for the 223 patients receiving gemcitabine was 13.6 months (95% CI, 12.3-15.3 months) and was 11.9 months (95% CI, 10.4-13.5 months) for the 219 patients receiving gemcitabine plus erlotinib (HR, 1.19; 95% CI, 0.97-1.45; P = .09; 188 deaths vs 191 deaths). Chemoradiotherapy was associated with decreased local progression (32% vs 46%, P = .03) and no increase in grade 3 to 4 toxicity, except for nausea. CONCLUSIONS AND RELEVANCE: In this open-label, randomized trial involving patients with locally advanced pancreatic cancer with disease controlled after 4 months of induction chemotherapy, there was no significant difference in overall survival with chemoradiotherapy compared with chemotherapy alone and there was no significant difference in overall survival with gemcitabine compared with gemcitabine plus erlotinib used as maintenance therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00634725.

6 Clinical Trial A randomized phase II study of weekly nab-paclitaxel plus gemcitabine or simplified LV5FU2 as first-line therapy in patients with metastatic pancreatic cancer: the AFUGEM GERCOR trial. 2015

Bachet, Jean-Baptiste / Chibaudel, Benoist / Bonnetain, Franck / Validire, Pierre / Hammel, Pascal / André, Thierry / Louvet, Christophe / Anonymous110845. ·Paris-Sorbonne University, UPMC University Paris 06, Paris, France. jean-baptiste.bachet@psl.aphp.fr. · Department of hepatogastroenterology, Groupe hospitalier Pitié Salpêtrière, Paris, France. jean-baptiste.bachet@psl.aphp.fr. · Department of oncology, Hôpital Saint Antoine, Paris, France. benoist.chibaudel@sat.aphp.fr. · Head of methodology and quality of life in oncology department, Hôpital Universitaire de Besancon, EA 3181, Besancon, France. franck.bonnetain@univ-fcomte.fr. · Department of pathology, Institut Mutualiste Montsouris, Paris, France. pierre.validire@imm.fr. · Department of digestive oncology, Hôpital Beaujon, Clichy, France. pascal.hammel@bjn.aphp.fr. · Paris-Sorbonne University, UPMC University Paris 06, Paris, France. thierry.andre@sat.aphp.fr. · Department of oncology, Hôpital Saint Antoine, Paris, France. thierry.andre@sat.aphp.fr. · Department of oncology, Institut Mutualiste Montsouris, Paris, France. christophe.louvet@imm.fr. ·BMC Cancer · Pubmed #26445094.

ABSTRACT: BACKGROUND: Metastatic pancreatic adenocarcinoma (PAC) prognosis remains dismal and gemcitabine monotherapy has been the standard treatment over the last decade. Currently, two first-line regimens are used in this setting: FOLFIRINOX and nab-paclitaxel plus gemcitabine. Increasing translational data on the predictive value of hENT1 for determining gemcitabine efficacy suggest that a non-gemcitabine-based regimen is favored in about 60 % of patients with PAC due to high resistance of PAC to this cytotoxic drug. This study aims to evaluate the efficacy of weekly nab-paclitaxel combined with gemcitabine or a simplified (s) LV5FU2 regimen in patients with previously untreated metastatic PAC. METHODS/DESIGN: AFUGEM is a two-stage, open-label, randomized, multicenter, phase II trial. Patients with PAC who meet the inclusion criteria and provide written informed consent will be randomized in a 1:2 ratio to either nab-paclitaxel (125 mg/m(2)) plus gemcitabine (1000 mg/m(2)) given on days 1, 8, and 15 every 28 days or nab-paclitaxel (125 mg/m(2)) plus sLV5FU2 (leucovorin 400 mg/m(2) followed by bolus 400 mg/m(2) 5-fluorouracil and by 5-fluorouracil 2400 mg/m(2) as an 46-h intravenous infusion) given on days 1 and 15 every 28 days. A total of 114 patients will be randomized to one of the treatment arms. The primary endpoint is progression-free survival at 4 months. Secondary outcomes are rate and duration of response, disease control, overall survival, safety, and quality of life. Potential biomarkers of gemcitabine (hENT1, dCK) and 5-fluorouracil (TS) efficacy will be assessed. DISCUSSION: The AFUGEM trial is designed to provide valuable information regarding efficacy and tolerability of nab-paclitaxel plus gemcitabine and nab-paclitaxel plus sLV5FU2 regimens. Identification of potential predictive biomarkers of gemcitabine and 5-fluorouracil is likely to drive therapeutic decisions in patients with metastatic PAC. TRIAL REGISTRATION: AFUGEM is registered at Clinicaltrials.gov: NCT01964534 , October 15, 2013.

7 Clinical Trial Circulating tumor cells in locally advanced pancreatic adenocarcinoma: the ancillary CirCe 07 study to the LAP 07 trial. 2013

Bidard, F C / Huguet, F / Louvet, C / Mineur, L / Bouché, O / Chibaudel, B / Artru, P / Desseigne, F / Bachet, J B / Mathiot, C / Pierga, J Y / Hammel, P. ·Department of Medical Oncology, Institut Curie, Paris, France. fcbidard@curie.fr ·Ann Oncol · Pubmed #23676420.

ABSTRACT: BACKGROUND: Pancreatic carcinoma is one of the leading causes of cancer-related mortality. At the time of diagnosis, 30% of patients present with a locally advanced pancreatic carcinoma (LAPC). As circulating tumor cells (CTCs) count may be a surrogate of the cancer metastatic abilities, CTC detection rates and prognostic value were studied in a prospective cohort of LAPC patients. PATIENTS AND METHODS: An LAP07 international multicenter randomized study assesses in patients whose LAPC is controlled after 4 months of chemotherapy whether chemoradiotherapy could increase survival versus continuation of chemotherapy. A subgroup of patients included in the LAP07 trial was screened for CTCs (CellSearch®) before the start of the chemotherapy and after 2 months of treatment. Patient characteristics and survival were obtained prospectively and were correlated with CTC detection. RESULTS: Seventy-nine patients were included. One or more CTCs/7.5 ml were detected in 5% of patients before treatment and in 9% of patients after 2 months of treatment (overall detection rate: 11% of patients). CTC positivity was associated with poor tumor differentiation (P = 0.04), and with shorter overall survival (OS) in multivariable analysis (RR = 2.5, P = 0.01), together with anemia. CONCLUSIONS: The evaluation of micrometastatic disease using CTC detection appears as a promising prognostic tool in LAPC patients.

8 Clinical Trial First-line simplified GEMOX (S-GemOx) versus classical GEMOX in metastatic pancreatic cancer (MPA): results of a GERCOR randomized phase II study. 2009

Afchain, P / Chibaudel, B / Lledo, G / Selle, F / Bengrine-Lefevre, L / Nguyen, S / Paitel, J-F / Mineur, L / Artru, P / André, T / Louvet, C. ·Service d'Oncologie, Hôpital Saint-Antoine, Assistance Publique des Hôpitaux de Paris, Paris, France. ·Bull Cancer · Pubmed #19435690.

ABSTRACT: PURPOSE: GemOx was defined as a D1-D2 schedule, based on preclinical data. In order to improve convenience for patients, we evaluated a simplified D1-D1 GemOx regimen (S-GemOx) in MPA. PATIENTS AND METHODS: Patients (pts) with MPA were 2:1 randomly assigned for first-line treatment to S-GemOx (gemcitabine 1,000 mg/m(2), 100-minute infusion D1 immediately followed by oxaliplatin 100 mg/m(2), 120-minute infusion) or to GemOx (Gem D1 and ox D2). Treatment was repeated in each arm every 2 weeks until disease progression. Stratification was performed on center and PS. RESULTS: Fifty-seven pts were enrolled, S-GemOx = 37 (PS 2: 22%), GemOx = 20 (PS 2: 20%). Populations were well balanced for age (64.9 vs 66.6 years); gender (57 vs 65% male), location of primary tumor (pancreas head: 49 vs 50%), and metastatic sites (liver 76 vs 85%; peritoneum 24 vs 20%; lung 16 vs 10%; lymph nodes 14 vs 15%; other 5 vs 5%). Tumor differentiation significantly differed between the 2 groups (S-GemOx: 8% poorly differentiated vs GemOx: 36%). Response rate was 27% (95% CI: 12-42) in arm S-GemOx and 10% (95% CI: 0-23) in GemOx. Median PFS was 4.0 and 2.5 months in S-GemOx and GemOx, respectively. Median OS was 7.6 and 3.2 months in S-GemOx and GemOx, respectively. Since more cycles were administered in S-GemOx (8.5 [1-29] vs 5.8 [2-12]), grade 3 oxaliplatin-induced neuropathy was higher in S-GemOx [21.6 vs 0%]). CONCLUSIONS: Activity and tolerance of S-GemOx are in the same range as compared to our previous experiences of classical GemOx in metastatic pancreatic cancer. The very bad outcome of patients randomized in GemOx arm could at least be in part explained by the high-rate of poorly differentiated tumors.

9 Article Time to health-related quality of life score deterioration as a modality of longitudinal analysis for health-related quality of life studies in oncology: do we need RECIST for quality of life to achieve standardization? 2015

Anota, Amélie / Hamidou, Zeinab / Paget-Bailly, Sophie / Chibaudel, Benoist / Bascoul-Mollevi, Caroline / Auquier, Pascal / Westeel, Virginie / Fiteni, Frederic / Borg, Christophe / Bonnetain, Franck. ·Quality of Life in Oncology Clinical Research Platform, Besançon, France, aanota@chu-besancon.fr. ·Qual Life Res · Pubmed #24277234.

ABSTRACT: PURPOSE: Longitudinal analysis of health-related quality of life (HRQoL) remains unstandardized and compromises comparison of results between trials. In oncology, despite available statistical approaches, results are poorly used to change standards of care, mainly due to lack of standardization and the ability to propose clinical meaningful results. In this context, the time to deterioration (TTD) has been proposed as a modality of longitudinal HRQoL analysis for cancer patients. As for tumor response and progression, we propose to develop RECIST criteria for HRQoL. METHODS: Several definitions of TTD are investigated in this paper. We applied this approach in early breast cancer and metastatic pancreatic cancer with a 5-point minimal clinically important difference. In breast cancer, TTD was defined as compared to the baseline score or to the best previous score. In pancreatic cancer (arm 1: gemcitabine with FOLFIRI.3, arm 2: gemcitabine alone), the time until definitive deterioration (TUDD) was investigated with or without death as event. RESULTS: In the breast cancer study, 381 women were included. The median TTD was influenced by the choice of the reference score. In pancreatic cancer study, 98 patients were enrolled. Patients in Arm 1 presented longer TUDD than those in Arm 2 for most of HRQoL scores. Results of TUDD were slightly different according to the definition of deterioration applied. CONCLUSION: Currently, the international ARCAD group supports the idea of developing RECIST for HRQoL in pancreatic and colorectal cancer with liver metastasis, with a view to using HRQoL as a co-primary endpoint along with a tumor parameter.