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Pancreatic Neoplasms: HELP
Articles by David Malka
Based on 13 articles published since 2010
(Why 13 articles?)
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Between 2010 and 2020, D. Malka wrote the following 13 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 An update on treatment options for pancreatic adenocarcinoma. 2019

Lambert, Aurélien / Schwarz, Lilian / Borbath, Ivan / Henry, Aline / Van Laethem, Jean-Luc / Malka, David / Ducreux, Michel / Conroy, Thierry. ·Department of Medical Oncology, Institut de Cancérologie de Lorraine and Université de Lorraine, Nancy, France. · Department of Digestive Surgery, Rouen University Hospital and Université de Rouen Normandie, France. · Department of Gastroenterology and Digestive Oncology, Cliniques Universitaires Saint-Luc and Université Catholique de Louvain, Brussels, Belgium. · Department of Supportive Care in Oncology, Institut de Cancérologie de Lorraine, Nancy, France. · Department of Gastroenterology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Belgium. · Department of Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France. · Institut de Cancérologie de Lorraine, 6 avenue de Bourgogne, 50519 Vandoeuvre-lès-Nancy CEDEX, France. ·Ther Adv Med Oncol · Pubmed #31598142.

ABSTRACT: Pancreatic cancer is one of the most lethal solid organ tumors. Due to the rising incidence, late diagnosis, and limited treatment options, it is expected to be the second leading cause of cancer deaths in high income countries in the next decade. The multidisciplinary treatment of this disease depends on the stage of cancer at diagnosis (resectable, borderline, locally advanced, and metastatic disease), and combines surgery, chemotherapy, chemoradiotherapy, and supportive care. The landscape of multidisciplinary pancreatic cancer treatment is changing rapidly, especially in locally advanced disease, and the number of treatment options in metastatic disease, including personalized medicine, innovative targets, immunotherapy, therapeutic vaccines, adoptive T-cell transfer, or stemness inhibitors, will probably expand in the near future. This review summarizes the current literature and provides an overview of how new therapies or new therapeutic strategies (neoadjuvant therapies, conversion surgery) will guide multidisciplinary disease management, future clinical trials, and, hopefully, will increase overall survival.

3 Review Systemic treatment of pancreatic cancer revisited. 2019

Ducreux, Michel / Seufferlein, Thomas / Van Laethem, Jean-Luc / Laurent-Puig, Pierre / Smolenschi, Cristina / Malka, David / Boige, Valérie / Hollebecque, Antoine / Conroy, Thierry. ·Département de Médecine Oncologique, Gustave Roussy Cancer Center Grand Paris, Université Paris Saclay, France. Electronic address: michel.ducreux@gustaveroussy.fr. · Department of Internal Medicine I, University of Ulm, Ulm, Germany. · Department of Gastroenterology and Digestive oncology, Erasme University Hospital, Université Libre de Bruxelles, Bruxelles, Belgium. · Assistance Publique-Hôpitaux de Paris, Department of Biology, European Georges Pompidou Hospital, Paris, France. · Département de Médecine Oncologique, Gustave Roussy Cancer Center Grand Paris, France. · Département de Médecine Oncologique, Gustave Roussy Cancer Center Grand Paris, France; Département d'Innovation Thérapeutique, Gustave Roussy Cancer Center Grand Paris, France. · Département d'oncologie médicale, Institut de Cancérologie de Lorraine, Université de Lorraine, Nancy, France. ·Semin Oncol · Pubmed #30638624.

ABSTRACT: Pancreatic cancer is considered to be one of the most aggressive cancers. For unknown reasons, the incidence of pancreatic cancer is slowly rising and so too are mortality rates. Over 75% of patients are diagnosed with locally advanced disease or with metastases; and more than 95% of patients have metastases at diagnosis or will develop metastases during their follow-up. Despite recent improvements in the therapy of pancreatic cancer, initially with demonstration of the activity of the FOLFIRINOX regimen and subsequently the approval of nab-paclitaxel in combination with gemcitabine, prognosis remains poor and the 5-year survival rate is less than 5%. To date, neither personalized medicine nor immunotherapy, the 2 recent revolutions of cancer treatment, have delivered major positive results in the treatment of pancreatic cancer; and it is especially clear that immune checkpoint inhibitors will not become a major tool in the treatment of pancreatic cancer. There are many ongoing studies, including those exploring combinations of chemotherapy with immunotherapy. Vaccines or T cells modified with a chimeric antigen receptor (CAR-T cells) could also play a role in the treatment of cancer in the future. The aim of this review is to discuss recent improvements in standard of care, major obstacles to overcome, recent results of new treatment combinations, and the most interesting innovative approaches.

4 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 / Anonymous1671149. ·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 .).

5 Clinical Trial Evaluating bevacizumab in combination with FOLFIRI after the failure of platinum-etoposide regimen in patients with advanced poorly differentiated neuroendocrine carcinoma: The PRODIGE 41-BEVANEC randomized phase II study. 2018

Walter, Thomas / Malka, David / Hentic, Olivia / Lombard-Bohas, Catherine / Le Malicot, Karine / Smith, Denis / Ferru, Aurélie / Assenat, Eric / Cadiot, Guillaume / Lievre, Astrid / Kurtz, Jean-Emmanuel / Dahan, Laetitia / Dubreuil, Olivier / Hautefeuille, Vincent / Lepere, Céline / Gangloff, Alice / Elhajbi, Farid / Coriat, Romain / Roquin, Guillaume / Bouarioua, Nadia / Granger, Victoire / Scoazec, Jean-Yves / Lepage, Côme. ·Department of Medical Oncology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France. Electronic address: thomas.walter@chu-lyon.fr. · Gastrointestinal Oncology Department, Gustave Roussy Institute, Villejuif, France. · Gastroenterology-Pancreatology Department, Beaujon Hospital, PMAD, Clichy, France. · Department of Medical Oncology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France. · Fédération Francophone de Cancérologie Digestive, Dijon, France. · Hepatogastroenterology and Digestive Oncology Department, Haut-Lévèque, University Hospital of Bordeaux, Pessac, France. · Pôle régional de cancérologie, University Hospital of Poitiers, Poitiers, France. · Medical Oncology Department, University Hospital St Eloi, Montpellier, France. · Department of Hepatogastroenterology and Digestive Oncology, Robert Debré Hospital, University Hospital of Reims, Reims, France. · Service des maladies de l'appareil digestif, University Hospital of Pontchaillou, Rennes, France. · Oncology Department, Nouvel Hospital Civil, University Hospital of Strasbourg, Strasbourg, France. · Digestive Oncology Department, University Hospital Timone, Marseille, France. · Hepatogastroenterology and Digestive Oncology Department, Pitié Salpêtrière Hospital, Paris, France. · Gastroenterology and Digestive Oncology, Amiens University Hospital, Amiens, France. · European Georges Pompidou Hospital, Paris, France. · Gastroenterology Department, University Hospital of Rouen, Rouen, France. · Oncology Department, Oscar Lambret Center, Lille, France. · Gastroenterology Department, Cochin Hospital, Paris, France. · Gastroenterology & Digestive Oncology, University Hospital of Angers, Angers, France. · Service de gastroentérologie et oncologie digestive, hôpital Nord, Saint Priest en Jarez, France. · Hepatogastroenterology Department, Michallon Hospital, University Hospital of Grenoble, Grenoble, France. · Gustave Roussy Cancer Campus, Department of Surgical and Molecular Pathology, Villejuif Cedex, France; Université Paris Saclay, Université Paris Sud XI, Faculté de Médecine de Bicêtre, Le Kremlin-Bicêtre, France. · Gastrointestinal Oncology Department, Gustave Roussy Institute, Villejuif, France; Gastroenterology & Digestive Oncology, University Hospital Le Bocage, Dijon, France. ·Dig Liver Dis · Pubmed #29258812.

ABSTRACT: INTRODUCTION: Patients with gastroenteropancreatic (GEP), metastatic or locally advanced, non-resectable, grade 3 poorly-differentiated neuroendocrine carcinoma (NEC) are treated with cisplatin (or carboplatin)-etoposide in first-line palliative chemotherapy (CT1). However, nearly all patients will develop resistance and there is no standard second-line treatment. AIM: PRODIGE 41-BEVANEC is an academic randomized, phase II study designed to evaluate the efficacy of bevacizumab in combination with FOLFIRI after failure of CT1 in unknown primary NEC and GEP-NEC. MATERIALS AND METHODS: The main eligibility criteria are age ≥18 years, metastatic (synchronous or metachronous) or locally advanced, non-resectable, grade 3 GEP-NEC, and documented progressive disease during or after CT1 therapy. RESULTS: A total of 124 patients will be randomly assigned (1:1) to receive either 5 mg/kg bevacizumab with FOLFIRI, or FOLFIRI alone, every 14 days until disease progression or unacceptable toxicity. The hypothesis is to demonstrate a 6-month overall survival for at least 50% of the patients in bevacizumab arm versus 35% in the control arm (FOLFIRI alone). Secondary endpoints are objective response, response duration, progression-free survival, toxicity, and biochemical response. CONCLUSION: The study is currently opened in France (NCT02820857). The first patient was randomized on September 6, 2017.

6 Clinical Trial Prognostic value of health-related quality of life in patients with metastatic pancreatic adenocarcinoma: a random forest methodology. 2016

Diouf, Momar / Filleron, Thomas / Pointet, Anne-Laure / Dupont-Gossard, Anne-Claire / Malka, David / Artru, Pascal / Gauthier, Mélanie / Lecomte, Thierry / Aparicio, Thomas / Thirot-Bidault, Anne / Lobry, Céline / Fein, Francine / Dubreuil, Olivier / Landi, Bruno / Zaanan, Aziz / Taieb, Julien / Bonnetain, Franck. ·Clinical Research and Innovation Directorate, Amiens University Hospital, Amiens, France. diouf.momar@chu-amiens.fr. · Methodology and Quality of Life in Oncology Unit, EA 3181 CHU Besançon and the Qualité de Vie et Cancer Clinical Research Platform, Besançon, France. diouf.momar@chu-amiens.fr. · Biostatistics Unit, Claudius Régaud Institute, Toulouse, France. · Hepatogastroenterology and Digestive Oncology Department, Hôpital Européen Georges Pompidou, Université Paris Descartes, Paris, France. · CHU Jean Minjoz, Besançon, France. · Gustave Roussy, Villejuif, France. · Hôpital Privé Jean Mermoz, Lyon, France. · Centre Georges-François Leclerc, Dijon, France. · CHU de Tours-Hôpital Trousseau, Chambray-Les-Tours, France. · CHU Avicenne, Université Paris 13, Sorbonne Paris Cité, Bobigny, France. · CHU Bicêtre, Le Kremlin-Bicêtre, France. · CHU Bichat-Claude Bernard, Paris, France. · Hepatogastroenterology and Digestive Oncology Department, Hôpital Européen Georges Pompidou, Université Paris Descartes, Paris, France. julien.taieb@egp.aphp.fr. · Methodology and Quality of Life in Oncology Unit, EA 3181 CHU Besançon and the Qualité de Vie et Cancer Clinical Research Platform, Besançon, France. ·Qual Life Res · Pubmed #26615615.

ABSTRACT: PURPOSE: Eastern Cooperative Oncology Group Performance Status (ECOG-PS) is currently an important parameter in the choice of treatment strategy for metastatic pancreatic adenocarcinoma (mPA) patients. However, previous research has shown that patients' self-reported health-related quality of life (HRQOL) scales provided additional prognostic information in homogeneous groups of patients with respect to ECOG-PS. The aim of this study was to identify HRQOL scales with independent prognostic value in mPA and to propose prognostic groups for these patients. METHODS: We analysed data from 98 chemotherapy-naive patients with histologically proven mPA recruited from 2007 to 2011 in the FIRGEM phase II study which aimed to compare the effectiveness of two chemotherapy regimen. HRQOL data were assessed with the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire. A random survival forest methodology was used to impute missing data and to identify major prognostic factors for overall survival. RESULTS: Baseline HRQOL assessment was completed by 60 % of patients (59/98). Twelve prognostic variables were identified. The three most important prognostic variables were fatigue, appetite loss, and role functioning, followed by three laboratory variables. The model's discriminative power assessed by Harrell's C statistic was 0.65. Fatigue score explained almost all the survival variability. CONCLUSION: HRQOL scores have prognostic value for mPA patients with good ECOG-PS. Moreover, the patient's fatigue, appetite loss, and self-perception of daily activities were more reliable prognostic indicators than clinical and laboratory variables. These HRQOL scores, especially the fatigue symptom, should be urgently included for prognostic assessment of mPA patients (with good ECOG-PS).

7 Clinical Trial Fixed-dose rate gemcitabine alone or alternating with FOLFIRI.3 (irinotecan, leucovorin and fluorouracil) in the first-line treatment of patients with metastatic pancreatic adenocarcinoma: an AGEO randomised phase II study (FIRGEM). 2014

Trouilloud, Isabelle / Dupont-Gossard, Anne-Claire / Malka, David / Artru, Pascal / Gauthier, Mélanie / Lecomte, Thierry / Aparicio, Thomas / Thirot-Bidault, Anne / Lobry, Céline / Asnacios, Amani / Manet-Lacombe, Sophie / Fein, Francine / Dubreuil, Olivier / Landi, Bruno / Zaanan, Aziz / Bonnetain, Franck / Taïeb, Julien. ·Hôpital Européen Georges Pompidou, Université Paris Descartes, Paris, France. · CHU Jean Minjoz, Besançon, France. · Gustave Roussy, Villejuif, France. · Hôpital Privé Jean Mermoz, Lyon, France. · Centre Georges-François Leclerc, Dijon, France. · CHU de Tours-Hôpital Trousseau, Chambray-Les-Tours, France. · CHU Avicenne, Université Paris 13, Sorbonne Paris Cité, Bobigny, France. · CHU Bicêtre, Le Kremlin-Bicêtre, France. · CHU Bichat-Claude Bernard, Paris, France. · CHU Antoine Béclère, Clamart, France. · Centre Hospitalier René Dubos, Cergy-Pontoise, France. · Hôpital Européen Georges Pompidou, Université Paris Descartes, Paris, France. Electronic address: julien.taieb@egp.aphp.fr. ·Eur J Cancer · Pubmed #25454414.

ABSTRACT: BACKGROUND: Fluorouracil and irinotecan-based, and gemcitabine-based regimens, are the standard of care in the first-line treatment of patients with metastatic pancreatic cancer. New approaches are needed to improve survival and quality of life. Whether a sequential approach alternating irinotecan, fluorouracil and gemcitabine may be effective and tolerable in patients with metastatic pancreatic cancer is unknown. METHODS: In this randomised, multicentre, open-label, phase 2 trial, patients with metastatic pancreatic adenocarcinoma, World Health Organisation (WHO) performance status 0-1, and bilirubin levels <1.5 upper limit of normal values (ULN) were randomised 1:1 to receive as first-line treatment either FOLFIRI.3 (irinotecan, leucovorin and fluorouracil) alternating with fixed-dose rate gemcitabine as 2-month periods (FIRGEM, arm A), or fixed-dose rate gemcitabine alone (arm B). Treatment was continued until disease progression or limiting toxicity. The primary end-point was the crude progression-free survival (PFS) rate at 6 months. The study is registered with EudraCT (N° 2006-005703-34). RESULTS: Between October 2007 and March 2011, 98 patients were enroled. The observed 6-month PFS rate was 43.5% (95% confidence interval (CI), [28.6-58.4%]) in arm A reaching the Fleming decision rules criteria to reject H0 and 26.1% (95% CI [12.9-39.3%]) in arm B. Objective response rates were 37% (23-51%) in arm A and 10% (1-19%) in arm B. Median PFS (5.0 versus 3.4 months, hazard ratio (HR)=0.59 [0.38-0.90]) and overall survival (11.0 versus 8.2 months, HR=0.71 [0.46-1.10]) were higher in arm A compared to arm B. The most frequent grade 3-4 toxicities were neutropenia (49%/24%; febrile neutropenia, 4%/0% in arms A/B), diarrhoea (arm A, 12% and arm B, 0%), and nausea/vomiting (8%/4%). No toxic deaths occurred. CONCLUSION: The FIRGEM strategy appears to be effective and feasible in patients with metastatic pancreatic cancer.

8 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 --

9 Article Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas: Are they really heterogeneous? Insights from the FFCD-GTE national cohort. 2017

Walter, T / Tougeron, D / Baudin, E / Le Malicot, K / Lecomte, T / Malka, D / Hentic, O / Manfredi, S / Bonnet, I / Guimbaud, R / Coriat, R / Lepère, C / Desauw, C / Thirot-Bidault, A / Dahan, L / Roquin, G / Aparicio, T / Legoux, J-L / Lombard-Bohas, C / Scoazec, J-Y / Lepage, C / Cadiot, G / Anonymous2580906. ·University Hospital, Lyon, France. Electronic address: thomas.walter@chu-lyon.fr. · University Hospital, Poitiers, France. · Gustave Roussy Institute, Villejuif, France. · FFCD, Dijon, France. · Trousseau Hospital, Tours, France. · Beaujon Hospital, Clichy, France. · University Hospital, Rennes, France. · Valenciennes Hospital, Valenciennes, France. · University Hospital, Toulouse, France. · Cochin Hospital, University Paris Descartes, Paris, France. · Georges Pompidou European Hospital, University Paris-V, Paris, France. · University Hospital, Lille, France. · Hôpitalde Bicêtre, Le Kremlin Bicêtre, France. · La Timone Hospital, Marseille, France. · University Hospital, Angers, France. · Avicenne Hospital, Bobigny, France. · Hôpital de la Source, Orléans, France. · University Hospital, Lyon, France. · FFCD, Dijon, France; University Hospital, Dijon, France. · University Hospital, Reims, France. ·Eur J Cancer · Pubmed #28501762.

ABSTRACT: BACKGROUND: Diagnosis and management of poorly differentiated gastro-entero-pancreatic (GEP) neuroendocrine carcinomas (NECs) remain challenging. Recent studies suggest prognostic heterogeneity. We designed within the French Group of Endocrine Tumours a prospective cohort to gain insight in the prognostic stratification and treatment of GEP-NEC. PATIENTS AND METHODS: All patients with a diagnosis of GEP-NEC between 1st January 2010 and 31st December 2013 could be included in this national cohort. Adenoneuroendocrine tumours were excluded. RESULTS: 253 patients from 49 centres were included. Median age was 66 years. Main primary locations were pancreas (21%), colorectal (27%), oesophagus-stomach (18%); primary location was unknown in 20%. Tumours were metastatic at diagnosis in 78% of cases. Performance status (PS) at diagnosis was 0-1 in 79% of patients. Among the 147 (58%) cases reviewed by an expert pathological network, 39% were classified as small cell NEC and 61% as large cell NEC. Median Ki67 index was 75% (range, 20-100). Median overall survival was 15.6 (13.6-17.0) months. Significant adverse prognostic factors in univariate analysis were PS > 1 (hazard ratio [HR] = 2.5), metastatic disease (HR = 1.6), NSE>2 upper limit of normal [ULN]; HR = 3.2), CgA>2 ULN (HR = 1.7) and lactate dehydrogenase >2 ULN (HR = 2.1). After first-line palliative chemotherapy (CT1) with platinum-etoposide (n = 152), objective response, progression-free survival and overall survival were 50%, 6.2 and 11.6 months; they were 24%, 2.9 and 5.9, respectively, after post-CT1 FOLFIRI regimen (n = 72). CONCLUSIONS: We report a large prospective series of GEP-NEC which show the predominance of large cell type and advanced stage at diagnosis. Prognosis was found more homogeneous than previously reported, mainly impacted by PS and tumour burden.

10 Article Not All Patients with a Pancreatic Neuroendocrine Tumour Will Benefit from All Approved or Recommended Therapeutic Options: A Real-Life Retrospective Study. 2017

Berdelou, Amandine / Boige, Valérie / Arfi-Rouche, Julia / Malka, David / Ederhy, Stéphane / Izzedine, Hassan / Leboulleux, Sophie / Chougnet, Cécile N / Burtin, Pascal / De Baere, Thierry / Laplanche, Agnès / Elias, Dominique / Schlumberger, Martin / Scoazec, Jean-Yves / Ducreux, Michel / Baudin, Eric. ·Department of Nuclear Medicine and Endocrine Tumours, Gustave Roussy, Université Paris XI, Villejuif, France. ·Neuroendocrinology · Pubmed #27225439.

ABSTRACT: BACKGROUND: At least nine therapeutic options are recommended or approved for pancreatic neuroendocrine tumour (pNET). The primary endpoint of this study was to determine the number of therapeutic lines given before death. Secondary endpoints were to determine toxic events as a function of number of therapeutic lines and of time. METHODS: Patients with pNET treated between 1998 and 2010 at our centre were characterised. All therapeutic lines were recorded as well as tumour- or toxic-related deaths. Persistent treatment-related toxicity (PTRT) was defined as: chronic kidney disease, anaemia, thrombocytopenia, neutropenia, severe liver failure, cardiac failure and recurrent sepsis, precluding at least one other therapeutic option or second cancers. RESULTS: Ninety-two patients were analysed. The median follow-up was 7 years. The 1-, 2- and 5-year overall survival rates were 90, 81 and 51%, respectively. After 3 and 5 therapeutic lines, 23 and 50% of patients had died, respectively. After 3 and 5 lines, the frequency of toxic events was 8 and 24%, respectively. Overall, 17 toxic events were observed including 6 treatment-related deaths and 11 PTRT. After 1, 2 and 5 years of treatment, the frequency of toxic events was 6, 9 and 16%, respectively. CONCLUSION: Tumour- and toxic-related deaths as well as PTRT may preclude access to all therapeutic options in patients with pNET. Optimised risk benefit sequence should be investigated.

11 Article FOLFIRINOX for locally advanced pancreatic adenocarcinoma: results of an AGEO multicenter prospective observational cohort. 2015

Marthey, L / Sa-Cunha, A / Blanc, J F / Gauthier, M / Cueff, A / Francois, E / Trouilloud, I / Malka, D / Bachet, J B / Coriat, R / Terrebonne, E / De La Fouchardière, C / Manfredi, S / Solub, D / Lécaille, C / Thirot Bidault, A / Carbonnel, F / Taieb, J. ·Department of Gastroenterology, Kremlin Bicêtre Hospital, Assistance publique-Hôpitaux de Paris (AP-HP), Paris Sud University, Le Kremlin Bicêtre, France. ·Ann Surg Oncol · Pubmed #25037971.

ABSTRACT: BACKGROUND: First-line treatment with FOLFIRINOX significantly increases overall survival (OS) in patients with metastatic pancreatic adenocarcinoma (PA) compared with gemcitabine. The aim of this observational cohort was to evaluate the tolerability and efficacy of this regimen in unresectable locally advanced PA (LAPA). PATIENTS AND METHODS: From February 2010 to February 2012, all consecutive patients from 11 French centers treated by FOLFIRINOX for a histologically proven LAPA were prospectively enrolled. Unresectability was defined independently by each center's multidisciplinary staff at diagnosis. Absence of metastatic disease was confirmed by chest-abdomen-pelvis computed tomography scan. FOLFIRINOX was delivered every 2 weeks as previously reported until progressive disease, major toxicity, or consolidation treatment by radiotherapy and/or surgery. RESULTS: Seventy-seven patients were enrolled. They received a median number of five cycles (1-30). Grade 3-4 toxicities were neutropenia (11 %), nausea (9 %), diarrhea (6 %), fatigue (6 %), and anemia (1 %). Grade 2-3 sensory neuropathy occurred in 25 % of patients. No toxic death was reported and only 6 % of patients had to stop treatment because of toxicity. Disease control rate was 84 with 28 % of objective response (Response Evaluation Criteria in Solid Tumors). Seventy-five percent of patients received a consolidation therapy: 70 % had radiotherapy and 36 % underwent a surgical resection, with a curative intent. Within the whole cohort, 1-year OS rate was 77 % (95 % CI 65-86) and 1-year progression-free survival rate was 59 % (95 % CI 46-70). CONCLUSION: First-line FOLFIRINOX for LAPA seems to be effective and have a manageable toxicity profile. These promising results will have to be confirmed in a phase III randomized trial.

12 Article Are G3 ENETS neuroendocrine neoplasms heterogeneous? 2013

Vélayoudom-Céphise, Fritz-Line / Duvillard, Pierre / Foucan, Lydia / Hadoux, Julien / Chougnet, Cecile N / Leboulleux, Sophie / Malka, David / Guigay, Joël / Goere, Diane / Debaere, Thierry / Caramella, Caroline / Schlumberger, Martin / Planchard, David / Elias, Dominique / Ducreux, Michel / Scoazec, Jean-Yves / Baudin, Eric. ·Department of Nuclear Medicine and Endocrine Oncology, Villejuif, France. ·Endocr Relat Cancer · Pubmed #23845449.

ABSTRACT: The new WHO classification of gastroenteropancreatic (GEP) neuroendocrine tumors (NET) implies that G3 neoplasms with mitotic index >20 and/or Ki67 index >20% are neuroendocrine carcinomas (NEC), described as poorly differentiated, small or large cell types, by analogy with lung NEC. To characterize the subgroup of non-small-cell-type GEP and thoracic NET with mitotic index >20 and/or Ki67 >20% according to their pathological features, response to cisplatin and overall survival (OS). We reviewed pathological and clinical presentation of G3 non-small-cell-type NET referred to our institution for 5 years. Data from 166 patients with metastatic thoracic and GEP-NET were collected. Twenty-eight patients (17%) fulfill the inclusion criteria. Tumors were classified as well-differentiated NET (G3-WDNET) in 42.8% of cases and poorly differentiated, large-cell NEC (G3-LCNEC) in 57.2% of cases. Plasma chromogranin A or neuron-specific enolase were elevated in 42 and 25% respectively of G3-WDNET and 31 and 50% of G3-LCNEC. Somatostatin receptor scintigraphy was positive in 88 and 50% of G3-WDNET or G3-LCNEC respectively. Complete or partial response to cisplatin was observed in 31% of cases, all classified as G3-LCNEC. The median OS was 41 months for G3-WDNET but 17 months for G3-LCNEC (P=0.34). Short survival was observed in 25% of G3-WDNET but 62.5% of G3-LCNEC patients (P=0.049). G3 ENETS GEP and thoracic neuroendocrine neoplasms (NEN) could constitute a heterogeneous subgroup of NEN as regards diagnosis, prognosis, and treatment. If confirmed, future classifications may consider splitting them into two groups according to their morphological differentiation.

13 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.

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