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1. Comparative Efficacy and Long-Term Oncological Safety of Extended Right Hemicolectomy Versus Left Colectomy for Splenic Flexure Adenocarcinoma: A Systematic Review and Meta-Analysis

Author: Mohamed Ali Chaouch, Bassem Krimi, Amine Gouader, Hanen Bhiri, Elise Barel, and Faiza Khemissa Akouz
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background Splenic flexure adenocarcinoma poses unique challenges in surgical management due to its location and lymphatic drainage. This study compared the efficacy and oncological safety of extended right hemicolectomy (ERC) and left colectomy (LC) for treating this condition. Methods This study followed the PRISMA and AMSTAR 2 guidelines. Key outcomes included postoperative mortality, morbidity, severe complications, operative results, pathological findings (R0 resection, lymph nodes), and oncological results (overall survival and disease-free survival at 3 and 5 years). Results Twelve non-randomised studies were included involving 1710 patients (713 ERC group, 997 LC group). The analysis showed that ERC was associated with more lymph nodes and a lower conversion rate. However, there were no significant differences between ERC and LC in terms of mortality, morbidity, severe complications, anastomotic leak, wound infection, ileus, reoperation, R0 resection, hospital stay, and overall and disease-free survival rates. Conclusions ERC and LC are comparable in terms of postoperative and long-term oncological outcomes for splenic flexure adenocarcinoma, with ERC potentially producing a higher lymph node harvest rate and a lower conversion rate. ERC could be suggested for a better stage of the disease and when the surgical team considers the laparoscopic approach.
Published: 2024
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2. Circulating Tumor Cells and Circulating Tumor DNA Detection in Potentially Resectable Metastatic Colorectal Cancer: A Prospective Ancillary Study to the Unicancer Prodige-14 Trial

Author: François-Clément Bidard, Nicolas Kiavue, Marc Ychou, Luc Cabel, Marc-Henri Stern, Jordan Madic, Adrien Saliou, Aurore Rampanou, Charles Decraene, Olivier Bouché, Michel Rivoire, François Ghiringhelli, Eric Francois, Rosine Guimbaud, Laurent Mineur, Faiza Khemissa-Akouz, Thibault Mazard, Driffa Moussata, Charlotte Proudhon, Jean-Yves Pierga, Trevor Stanbury, Simon Thézenas, and Pascale Mariani
Subjects: circulating tumor cells, circulating tumor DNA, liquid biopsy, metastatic colorectal cancer, FOLFIRINOX, Cytology, QH573-671
Abstract: The management of patients with colorectal cancer (CRC) and potentially resectable liver metastases (LM) requires quick assessment of mutational status and of response to pre-operative systemic therapy. In a prospective phase II trial (NCT01442935), we investigated the clinical validity of circulating tumor cell (CTC) and circulating tumor DNA (ctDNA) detection. CRC patients with potentially resectable LM were treated with first-line triplet or doublet chemotherapy combined with targeted therapy. CTC (Cellsearch®) and Kirsten RAt Sarcoma (KRAS) ctDNA (droplet digital polymerase chain reaction (PCR)) levels were assessed at inclusion, after 4 weeks of therapy and before LM surgery. 153 patients were enrolled. The proportion of patients with high CTC counts (≥3 CTC/7.5mL) decreased during therapy: 19% (25/132) at baseline, 3% (3/108) at week 4 and 0/57 before surgery. ctDNA detection sensitivity at baseline was 91% (N=42/46) and also decreased during treatment. Interestingly, persistently detectable KRAS ctDNA (p = 0.01) at 4 weeks was associated with a lower R0/R1 LM resection rate. Among patients who had a R0/R1 LM resection, those with detectable ctDNA levels before liver surgery had a shorter overall survival (p < 0.001). In CRC patients with limited metastatic spread, ctDNA could be used as liquid biopsy tool. Therefore, ctDNA detection could help to select patients eligible for LM resection.
Published: 2019
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3. Phase III randomized trial comparing systemic versus intra-arterial oxaliplatin, combined with LV5FU2 +/- irinotecan and a targeted therapy, in the first-line treatment of metastatic colorectal cancer restricted to the liver (OSCAR): PRODIGE 49

Author: Simon Pernot, Olivier Pellerin, Laurent Mineur, Carole Monterymard, Denis Smith, Bruno Lapuyade, Claire Gallois, Faiza Khemissa Akouz, Thierry De Baere, David Tougeron, Anne Thirot-Bidault, Franck Audemar, Mireille Simon, Cedric Lecaille, Sami Louafi, Come Lepage, Michel Ducreux, and Julien Taieb
Subjects: Organoplatinum Compounds, Hepatology, Liver Neoplasms, Leucovorin, Gastroenterology, Bevacizumab, Oxaliplatin, Hepatic Artery, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols, Humans, Infusions, Intra-Arterial, Fluorouracil, Colorectal Neoplasms
Abstract: In patients with unresectable liver metastases from colorectal cancer (CRCLM), systemic doublet or triplet chemotherapy and targeted therapy is considered a standard first-line treatment. Hepatic arterial infusion of oxaliplatin (HAI-ox) generates a high response rate, but this still needs to be confirmed in a randomized trial. We incorporated HAI-ox in doublet or triplet + targeted therapy to validate its efficacy.The OSCAR study is an ongoing randomized phase III trial comparing FOLFOX + targeted therapy according to RAS status, or FOLFOXIRI + bevacizumab in patients eligible for triplet therapy, with the same regimen but with HAI-ox instead of IV-ox as the first-line treatment for CRCLM.Main eligibility criteria are colorectal cancer, unresectable liver metastasis, no extra-hepatic metastases except pulmonary nodules if ≤3 and10 mm, ECOG performance status 0 or 1.The primary endpoint is progression-free survival (PFS). A difference of 4 months for the median PFS in favor of HAI-ox is expected (HR = 0.73). Secondary endpoints include overall survival, overall response rate, secondary liver resection, safety, and quality of life.This study is planned to include 348 patients to demonstrate the superiority of HAI-ox over systemic oxaliplatin in first-line CRCLM treatment (NCT02885753).
Published: 2022
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4. Modified FOLFIRINOX Versus CISGEM Chemotherapy for Patients With Advanced Biliary Tract Cancer (PRODIGE 38 AMEBICA): A Randomized Phase II Study

Author: Sylvain Manfredi, Eric Terrebonne, David Malka, Prodige Investigators, Emilie Barbier, Valérie Lebrun Ly, Hervé Perrier, Laetitia Dahan, François Ghiringhelli, Faiza Khemissa Akouz, Emilie Soularue, Thierry Lecomte, Cindy Neuzillet, Jean-Marc Phelip, Yann Molin, Vincent Bourgeois, Samy Louafi, Julien Edeline, Romain Coriat, Jérôme Desramé, and Pierre Michel
Subjects: Cancer Research, Chemotherapy, medicine.medical_specialty, Biliary tract cancer, business.industry, FOLFIRINOX, medicine.medical_treatment, Phases of clinical research, Gastroenterology, Oncology, Triplet chemotherapy, Internal medicine, Medicine, business
Abstract: PURPOSE Whether triplet chemotherapy is superior to doublet chemotherapy in advanced biliary tract cancer (BTC) is unknown. METHODS In this open-label, randomized phase II-III study, patients with locally advanced or metastatic BTC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (1:1) to receive oxaliplatin, irinotecan, and infusional fluorouracil (mFOLFIRINOX), or cisplatin and gemcitabine (CISGEM) for a maximum of 6 months. We report the results of the phase II part, where the primary end point was the 6-month progression-free survival (PFS) rate among the patients who received at least one dose of treatment (modified intention-to-treat population) according to Response Evaluation Criteria in Solid Tumors version 1.1 (statistical assumptions: 6-month PFS rate ≥ 59%, 73% expected). RESULTS A total of 191 patients (modified intention-to-treat population, 185: mFOLFIRINOX, 92; CISGEM, 93) were randomly assigned in 43 French centers. After a median follow-up of 21 months, the 6-month PFS rate was 44.6% (90% CI, 35.7 to 53.7) in the mFOLFIRINOX arm and 47.3% (90% CI, 38.4 to 56.3) in the CISGEM arm. Median PFS was 6.2 months (95% CI, 5.5 to 7.8) in the mFOLFIRINOX arm and 7.4 months (95% CI, 5.6 to 8.7) in the CISGEM arm. Median overall survival was 11.7 months (95% CI, 9.5 to 14.2) in the mFOLFIRINOX arm and 13.8 months (95% CI, 10.9 to 16.1) in the CISGEM arm. Adverse events ≥ grade 3 occurred in 72.8% of patients in the mFOLFIRINOX arm and 72.0% of patients in the CISGEM arm (toxic deaths: mFOLFIRINOX arm, two; CISGEM arm, one). CONCLUSION mFOLFIRINOX triplet chemotherapy did not meet the primary study end point. CISGEM doublet chemotherapy remains the first-line standard in advanced BTC.
Published: 2022
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5. Chemotherapy (doublet or triplet) plus targeted therapy by RAS status as conversion therapy in colorectal cancer patients with initially unresectable liver-only metastases. The UNICANCER PRODIGE-14 randomised clinical trial

Author: Marc Ychou, Michel Rivoire, Simon Thezenas, Rosine Guimbaud, Francois Ghiringhelli, Anne Mercier-Blas, Laurent Mineur, Eric Francois, Faiza Khemissa, Marion Chauvenet, Reza Kianmanesh, Marianne Fonck, Philippe Houyau, Thomas Aparicio, Marie-Pierre Galais, Franck Audemar, Eric Assenat, Evelyne Lopez-Crapez, Claire Jouffroy, Antoine Adenis, René Adam, and Olivier Bouché
Subjects: Male, Cancer Research, Liver Neoplasms, Leucovorin, Cetuximab, Middle Aged, Article, Bevacizumab, Pancreatic Neoplasms, Oncology, Antineoplastic Combined Chemotherapy Protocols, Humans, Camptothecin, Fluorouracil, Colorectal Neoplasms
Abstract: BACKGROUND: Colorectal cancer (CRC) patients have a better prognosis if metastases are resectable. Initially, unresectable liver-only metastases can be converted to resectable with chemotherapy plus a targeted therapy. We assessed which of chemotherapy doublet (2-CTx) or triplet (3-CTx), combined with targeted therapy by RAS status, would be better in this setting. METHODS: PRODIGE 14 was an open-label, multicenter, randomised Phase 2 trial. CRC patients with initially defined unresectable liver-only metastases received either, 2-CTx (FOLFOX or FOLFIRI) or 3-CTx (FOLFIRINOX), plus bevacizumab/cetuximab by RAS status. The primary endpoint was to increase the R0/R1 liver-resection rate from 50 to 70% with the 3-CTx. RESULTS: Patients (n = 256) were mainly men with an ECOG PS of 0, and a median age of 60 years. In total, 109 patients (42.6%) had RAS-mutated tumours. After a median follow-up of 45.6 months, the R0/R1 liver-resection rate was 56.9% (95% CI: 48–66) with the 3-CTx versus 48.4% (95% CI: 39–57) with the 2-CTx (P = 0.17). Median overall survival was 43.4 months with 3-CTx versus 40 months with 2-CTx. CONCLUSION: We failed to increase from 50 to 70% the R0/R1 liver-resection rate with the use of 3-CTx combined with bevacizumab or cetuximab by RAS status in CRC patients with initially unresectable liver metastases.
Published: 2022
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6. Gemcitabine plus nab-paclitaxel until progression or alternating with FOLFIRI.3, as first-line treatment for patients with metastatic pancreatic adenocarcinoma: The Federation Francophone de Cancérologie Digestive-PRODIGE 37 randomised phase II study (FIRGEMAX)

Author: David Malka, Benoît Dupont, Alain Gratet, Pamela Biondiani, Marion Chauvenet, Dany Gargot, Pierre-Emmanuel Henneresse, Hortense Laharie, Johann Dreanic, Valérie Lebrun Lyat, Catherine Brezault-Bonnet, Morgan Andre, Géraldine Perkins, Philippe Houyau, Yves Rinaldi, Etienne Suc, Dominique Besson, Valérie Boige, Cécile Julien, Julien Taieb, Simon Pernot, Benoît Avisse, Pauline Regnault, Ahmed Bedjaoui, Marie-Pierre Galais, Côme Lepage, Céline Lepère, Mme E. Barbier, Antoine Holllebecque, Anne Escande, Julie Vincent, Sandrine Lavau denes, Marie-Claude Gouttebel, Leila Bengrine Lefevre, Anne Thirot Bidault, Anne-Laure Pointet, Julie Gigout, Faiza Khemissa Akouz, Louis-Marie Dourthe, Frederick Moryoussef, Maxime Lesouef, Vincent Bourgeois, François Ghiringhelli, Patrick Texereau, Samy Louafi, Gildas Phelip, Yann Berge, Jean-François Codoul, Jérôme Chamois, Eric Terrebonne, Karine Bouhier Leporrier, Bidaut Wahiba, X. Artignan, Pr Pierre Michel, Iulia Pripon, David Sefrioui, Pierre-Luc Etienne, Romain Coriat, Aurélie Parzy, Mustapha Atlassi, Aziz Zaanan, Jean-Baptiste Bachet, Philippe Dominici, Jean Martin, Mathilde Martinez, Dominique Genet, Raymond Despax, Karine Le Malicot, Laurent Miglianico, Salvatore Caruso, Bruno Valenza, Nicolas Barriere, and Oana Zveltlana Cojocarasu
Subjects: Adult, Male, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Paclitaxel, Population, Leucovorin, Phases of clinical research, Adenocarcinoma, Neutropenia, Irinotecan, Deoxycytidine, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Albumins, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Neoplasm Metastasis, education, Aged, education.field_of_study, Drug Substitution, business.industry, Middle Aged, medicine.disease, Gemcitabine, Neoadjuvant Therapy, Progression-Free Survival, Pancreatic Neoplasms, Treatment Outcome, 030104 developmental biology, Oncology, Tolerability, 030220 oncology & carcinogenesis, Disease Progression, FOLFIRI, Camptothecin, Female, Fluorouracil, France, business, Febrile neutropenia, medicine.drug
Abstract: Background Chemotherapy is effective in metastatic pancreatic adenocarcinoma (mPA), but new approaches are still needed to improve patients' survival and quality of life. We have previously published good efficacy and tolerability results on a sequential treatment strategy of gemcitabine followed by an intensified FOLFIRI (5FU+irinotecan) regimen. In the present study, we evaluated the same sequence but replaced gemcitabine by the new gemcitabine + nab-paclitaxel standard first-line combination. Patients and methods We randomised chemotherapy-naive patients with proven mPA, bilirubin levels ≤1.5 upper limit of normal values and performance status 0–2 to alternately receive gemcitabine + nab-paclitaxel for 2 months then FOLFIRI.3 for 2 months in arm A, or gemcitabine + nab-paclitaxel alone until progression in arm B. The primary objective was to increase the 6-month progression-free survival (PFS) rate from 40% (H0) to 60% (H1); using the binomial exact method, 124 patients were required. Analyses were carried out in preplanned modified intention-to-treat (mITT) and per-protocol (PP) populations. Results Between November 2015 and November 2016, 127 patients were enrolled. Main grade III–IV toxicities (% in arm A/B) were: diarrhoea (12.5/1.7), neutropenia (46.9/31, including febrile neutropenia: 1.6/0), skin toxicity (6.3/13.8), and peripheral neuropathy (6.3/8.6). No toxic deaths occurred. The objective response rate was 40.3% (95% confidence interval [CI]: 28.1–53.6) in arm A and 26.7% (95% CI: 16.1–39.7) in arm B. The primary end-point (6-month PFS rate) was 45.2% [one-sided 95% CI: 34.3–56.4] in arm A and 23.3% in arm B [one-sided 95% CI: 14.3–32.3] in the mITT population. In the PP population, median PFS and OS were 7.6 months and 6 months and 14.5 months and 12.2 months in arm A and B, respectively. Conclusions The FIRGEMAX strategy with gemcitabine + nab-paclitaxel alternating with FOLFIRI.3 every 2 months, appears feasible and effective, with manageable toxicities, in patients able to reach >2mo of treatment. Trial registration information EudraCT: 2014-004449-28: NCT: 0282701.
Published: 2020
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7. Regorafenib (REG) combined with irinotecan (IRI) versus IRI alone as second-line treatment in patients with metastatic gastro-oesophageal adenocarcinomas (mGA): A randomized phase II trial (PRODIGE 58 – UCGI 35 – REGIRI)

Author: Emmanuelle Samalin, Hélène Senellart, Ludovic Evesque, Olivier Bouché, Faiza Khemissa, Christelle De La Fouchardiere, Anthony Lopez, Slimane Dermeche, Damien Botsen, David Tougeron, Aziz Zaanan, Meher BEN Abdelghani, Emmanuel Guardiola, Olivier Dubreuil, Valérie Le Brun Ly, Audrey Hennequin, Nicolas De Sousa Carvalho, Florence Castan, and Anthony Turpin
Subjects: Cancer Research, Oncology
Abstract: 387 Background: Several options have been evaluated as 2nd line treatment in mGA after failure of 1st line platinum based chemotherapy including taxanes and IRI as monotherapies or paclitaxel combined with ramucirumab but with a limited efficacy. REG monotherapy showed promising efficacy as 2nd or 3rd line treatment in mGA (Pavlakis N et al, J Clin Oncol. 2016). Methods: This comparative phase 2 multicenter randomized study was designed to evaluate the safety and efficacy of REG + IRI (REGIRI) vs IRI alone as 2nd line treatment in MGA patients (pts). Key eligibility criteria were histologically proven mGA (gastric or gastroesophageal junction (GEJ) tumor Siewert II and III), fluoropyrimidine and platinum-based first-line chemotherapy and ECOG PS ≤1. Pts received IRI 180 mg/m2 IV on D1 and D15. In REGIRI arm REG 160 mg/day was added on D2-D8 and D16-D22 every 28 days. Primary endpoint was overall survival (OS). A total of 122 events (154 pts) were required based on an assumption of 4-month (mo) gain in median OS (from 6 to 10 mo, HR=0.60), with a preplanned interim analysis of safety after 38 pts and efficacy after 40 OS events. Genotyping of cyclin-D1 was performed to evaluate the impact of treatment efficacy. Results: A total of 89 patients (REGIRI, n=44; IRI, n=45) with median age of 62 (range: 28-82) years and a mGA (67.4% with GEJ, 22.8% HER2+) were included out of the 154 initially planned by 21 sites in France. Study was prematurely stopped after interim analysis for unfavourable efficacy/toxicity ratio. With a median follow-up of 19.4 mo, 79 OS events were observed and median OS was 6.3 mo (95%CI[5.2-7.1]) with REGIRI vs 8.2 mo (95%CI[5.2-9.7]) with IRI (HR=1.11 CI95%[0.70-1.74], p=0.66). Median PFS was 2.2 mo vs 1.9 mo (NS) with REGIRI and IRI, respectively. Objective response rate was 15.9% and 13.3% respectively. Disease control rate was 45.5% and 33.3%. AEs grade ≥ 3 related to treatment were reported in 52.3% of pts in REGIRI arm vs 23.3% in IRI arm with 4 toxic deaths (diarrhea, sepsis and thromboembolic events) vs 1 (primary tumour perforation), respectively. The main severe toxicities were diarrhea: 18.2% vs 7% and febrile neutropenia: 8.2% vs 0%. Genotyping of cyclin D1 was performed on 72 pts: 19 presented A/A genotype, 38 A/G and 15 G/G. There were no differences in terms of OS according to genotyping. Conclusions: PRODIGE58/REGIRI trial was prematurely stopped after the interim analysis due to high toxicities reported in REGIRI arm with negative results on its primary endpoint. Further ancillary analysis are expected to identify toxicity risk factors and pts subgroups benefit with this combination. Clinical trial information: NCT03722108 .
Published: 2023
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8. LEANOX: Lean body mass normalization of oxaliplatin-based chemotherapy for patients with stage III colon cancer treated in adjuvant setting: Impact on oxaliplatin-induced sensitive neurotoxicity—A multicenter phase II randomized trial

Author: Eric Assenat, Meher BEN Abdelghani, Maeva Monnier, Herve Perrier, Faiza Khemissa, Romain Desgrippes, Marie-Pierre Galais, Yves Rinaldi, Come Lepage, Raphael Tetreau, and Pierre Senesse
Subjects: Cancer Research, Oncology
Abstract: 92 Background: Adjuvant chemotherapy is the current worldwide standard of care for stage III colorectal cancer (CRC) but it leads to significant neurotoxicity. We have shown in 2 cohorts of CRC patients treated with Oxaliplatin (Ox) that Ox-due neuropathy occurred in patients receiving an excess of 3.09 mg Ox/ kg Lean Body Mass (LBM). The aim of this trial was to determine whether the Ox dose adaptation based on the LBM index can reduce neurotoxicity, in patients treated for a stage III CRC. Methods: LEANOX is a randomized phase II multicentre study in patients eligible for an Ox regimen as adjuvant chemotherapy for CRC. Patients without sarcopenia (LBM index
Published: 2023
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9. Early evaluation using a radiomic signature of unresectable hepatic metastases to predict outcome in patients with colorectal cancer treated with FOLFIRI and bevacizumab

Author: Anthony, Dohan, Benoit, Gallix, Boris, Guiu, Karine, Le Malicot, Caroline, Reinhold, Philippe, Soyer, Jaafar, Bennouna, Francois, Ghiringhelli, Emilie, Barbier, Valérie, Boige, Julien, Taieb, Olivier, Bouché, Eric, François, Jean-Marc, Phelip, Christian, Borel, Roger, Faroux, Jean-Francois, Seitz, Stéphane, Jacquot, Meher, Ben Abdelghani, Faiza, Khemissa-Akouz, Dominique, Genet, Jean Louis, Jouve, Yves, Rinaldi, Françoise, Desseigne, Patrick, Texereau, Etienne, Suc, Come, Lepage, Thomas, Aparicio, Christine, Hoeffel, Zied, Ladhib, Service de Radiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), McGill University Health Center [Montreal] (MUHC), l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD), CHU Strasbourg, Département radiologie diagnostique et interventionnelle Saint Eloi [CHRU Montpellier], Pôle Digestif [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Fédération Francophone de la Cancérologie Digestive, FFCD, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Equipe EPICAD (LNC - U1231), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut Gustave Roussy (IGR), Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Paul Strauss, CRLCC Paul Strauss, Service de chirurgie digestive (CH de La Roche-sur-Yon), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Cancérologie du Grand Montpellier (CCGM), Centre Hospitalier Saint Jean de Perpignan, Polyclinique de Limoges - site François Chénieux [Limoges], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Européen [Fondation Ambroise Paré - Marseille], Centre Léon Bérard [Lyon], CHU Mont de Marsan, Clinique Saint-Jean Languedoc [Toulouse] (CSJL), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre de Recherche en Sciences et Technologies de l'Information et de la Communication - EA 3804 (CRESTIC), Université de Reims Champagne-Ardenne (URCA), and Hôpital Maison Blanche
Subjects: Male, Oncology, Colorectal cancer, medicine.medical_treatment, Leucovorin, Kaplan-Meier Estimate, 030218 nuclear medicine & medical imaging, MESH: Camptothecin / administration & dosage, Camptothecin / analogs & derivatives, Colorectal Neoplasms / drug therapy, Colorectal Neoplasms / pathology, Computational Biology, Female, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, Prospective cohort study, Aged, 80 and over, Liver Neoplasms, Gastroenterology, MESH: Radiographic Image Interpretation, Computer-Assisted, Response Evaluation Criteria in Solid Tumors, Survival Rate, Tomography, X-Ray Computed, Middle Aged, Bevacizumab, 030220 oncology & carcinogenesis, Cohort, FOLFIRI, Radiographic Image Interpretation, Computer-Assisted, Fluorouracil, Colorectal Neoplasms, Clinical decision making, medicine.drug, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Fluorouracil / administration & dosage, Humans, Leucovorin / administration & dosage, Liver Neoplasms / diagnostic imaging, Computerised image analysis, 03 medical and health sciences, Colorectal metastases, MESH: Adult, Antineoplastic Combined Chemotherapy Protocols / administration & dosage, Bevacizumab / administration & dosage, Camptothecin / administration & dosage, Predictive Value of Tests, Internal medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Chemotherapy, MESH: Liver Neoplasms / secondary, Aged, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Log-rank test, Irinotecan, Camptothecin, business
Abstract: PurposeThe objective of this study was to build and validate a radiomic signature to predict early a poor outcome using baseline and 2-month evaluation CT and to compare it to the RECIST1·1 and morphological criteria defined by changes in homogeneity and borders.MethodsThis study is an ancillary study from the PRODIGE-9 multicentre prospective study for which 491 patients with metastatic colorectal cancer (mCRC) treated by 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) and bevacizumab had been analysed. In 230 patients, computed texture analysis was performed on the dominant liver lesion (DLL) at baseline and 2 months after chemotherapy. RECIST1·1 evaluation was performed at 6 months. A radiomic signature (Survival PrEdiction in patients treated by FOLFIRI and bevacizumab for mCRC using contrast-enhanced CT TextuRe Analysis (SPECTRA) Score) combining the significant predictive features was built using multivariable Cox analysis in 120 patients, then locked, and validated in 110 patients. Overall survival (OS) was estimated with the Kaplan-Meier method and compared between groups with the logrank test. An external validation was performed in another cohort of 40 patients from the PRODIGE 20 Trial.ResultsIn the training cohort, the significant predictive features for OS were: decrease in sum of the target liver lesions (STL), (adjusted hasard-ratio(aHR)=13·7, p=1·93×10–7), decrease in kurtosis (ssf=4) (aHR=1·08, p=0·001) and high baseline density of DLL, (aHR=0·98, p0·02 had a lower OS in the training cohort (pConclusionA radiomic signature (combining decrease in STL, density and computed texture analysis of the DLL) at baseline and 2-month CT was able to predict OS, and identify good responders better than RECIST1.1 criteria in patients with mCRC treated by FOLFIRI and bevacizumab as a first-line treatment. This tool should now be validated by further prospective studies.Trial registrationClinicaltrial.gov identifier of the PRODIGE 9 study: NCT00952029.Clinicaltrial.gov identifier of the PRODIGE 20 study: NCT01900717.
Published: 2019
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10. 508TiP PRODIGE 68 - UCGI 38 - SOREGATT: A randomized phase II study comparing the sequences of regorafenib (reg) and trifluridine/tipiracil (t/t) after failure of standard therapies in patients (pts) with metastatic colorectal cancer (mCRC)

Author: D. Pannier, Julien Taieb, Anne-Laure Villing, Damien Botsen, H. Alexandre, J-B. Bachet, M. Ben Abdelghani, M-L. Tanguy, Jerome Martin-Babau, F. Garic, A. Parzy, David Tougeron, A. Peytier, O. Bouche, Michel Ducreux, Faiza Khemissa, and J. Viaud
Subjects: Oncology, medicine.medical_specialty, business.industry, Colorectal cancer, Phases of clinical research, Hematology, medicine.disease, chemistry.chemical_compound, chemistry, Internal medicine, Regorafenib, medicine, In patient, business
Published: 2021
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11. Phase 2 trial comparing sorafenib, pravastatin, their combination or supportive care in HCC with Child-Pugh B cirrhosis

Author: Jean-Frédéric, Blanc, Faiza, Khemissa, Jean-Pierre, Bronowicki, Carole, Monterymard, Jean-Marc, Perarnau, Vincent, Bourgeois, Stéphane, Obled, Meher Ben, Abdelghani, Isabelle, Mabile-Archambeaud, Roger, Faroux, Jean-François, Seitz, Christophe, Locher, Hélène, Senellart, Anne-Laure, Villing, Franck, Audemar, Charlotte, Costentin, Gaël, Deplanque, Sylvain, Manfredi, Julien, Edeline, and Youssef, Tazi
Subjects: Liver Cirrhosis, Niacinamide, Drug Combinations, Carcinoma, Hepatocellular, Treatment Outcome, Phenylurea Compounds, Liver Neoplasms, Humans, Antineoplastic Agents, Prospective Studies, Sorafenib, Pravastatin
Abstract: There is limited data regarding the role for systemic treatment in patients with Hepatocellular Carcinoma with Child-Pugh B cirrhosis.PRODIGE 21 was a multicentric prospective non-comparative randomized trial. Patients were randomized to receive sorafenib (Arm A), pravastatin (Arm B), sorafenib-pravastatin (Arm C) combination, or best supportive care (Arm D). Primary endpoint was time to progression (TTP), secondary endpoints included safety and overall survival (OS).160 patients were randomized and 157 patients were included in the final analysis. 86% of patients were BCLC C and 55% had macrovascular invasion. The safety profiles of the drugs were as expected. Median TTP was 3.5, 2.8, 2.0 and 2.2 months in arms A, B, C and D, respectively, but analysis was limited by the number of patients deceased without radiological progression (59%). Median OS was similar between the four arms: 3.8 [95% CI: 2.4-6.5], 3.1 [95% CI: 1.9-4.3], 4.0 [95% CI: 3.2-5.5] and 3.5 months [95% CI: 2.2-5.4] in arms A, B, C and D, respectively. Median OS was 4.0 months [95% CI: 3.3-5.5] for patients treated with sorafenib, vs 2.9 months [95% CI: 2.2-3.9] for patients not treated with sorafenib. In patients with ALBI grade 1/2, median OS was 6.1 months [95% CI: 3.8-8.3] in patients treated with sorafenib vs 3.1 months [95% CI: 1.9-4.8] for patients not treated with sorafenib.In the overall Child-Pugh B population, neither sorafenib nor pravastatin seemed to provide benefit. In the ALBI grade 1/2 sub-population, our trial suggests potential benefit of sorafenib.The study was referenced in clinicaltrials.gov (NCT01357486).
Published: 2020

12. Single-arm phase II trial to evaluate efficacy and tolerance of regorafenib monotherapy in patients over 70 with previously treated metastatic colorectal adenocarcinoma FFCD 1404 - REGOLD

Author: Gaetan Des Guetz, Thomas Aparicio, Denis Smith, Bruno Valenza, Nathalie Baize, Côme Lepage, Catherine Delbaldo, Denis Père Verge, Olivier Romano, Frédéric Pamoukdjian, Emmanuelle Norguet Monnereau, Anthony Dohan, Claire Falandry, L. Cany, Ariane Darut-Jouve, Christine Le Foll, Pascal Artru, Yves Rinaldi, Carole Monterymard, E. Maillard, Meher Ben Abdelghani, Faiza Khemissa Akouz, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinique Drévon, Service de hépato-gastro-entérologie - cancérologie digestive [CH de Perpignan], Centre Hospitalier Saint Jean de Perpignan, Fédération Francophone de la Cancérologie Digestive, FFCD, Service Biostatistiques et Informatique Médicale (CHU de Dijon) (DIM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Clinique Jean-Mermoz, Hôpital privé Jean Mermoz, Polyclinique Francheville, Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe Hospitalier Diaconesses Croix Saint-Simon, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), CRLCC Paul Strauss, IRCER - Axe 1 : procédés céramiques (IRCER-AXE1), Institut de Recherche sur les CERamiques (IRCER), Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service de gastro-entérologie (Hôpital Européen de Marseille), Hôpital Européen [Fondation Ambroise Paré - Marseille], Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Institut de Cancérologie de Bourgogne, Hôpital privé Jean Mermoz [Lyon], Clinique Francheville [Périgueux], Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Intercommunal Fréjus - St Raphaël (CHI Fréjus - St Raphaël), Grand Hôpital de l'Est Francilien (GHEF), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Bordeaux [Bordeaux], Hôpital Européen de Marseille (HEM), Service de Gastro entérologie [Hôpital Paris Saint-Joseph], Hôpital Paris Saint-Joseph, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Hôpital Cochin [AP-HP], Hôpital Dupuytren [CHU Limoges], Hôpital Avicenne [AP-HP], Equipe EPICAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), CCSD, Accord Elsevier, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: medicine.medical_specialty, Colorectal cancer, Pyridines, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Adenocarcinoma, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Quality of life, Regorafenib, Internal medicine, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, Adverse effect, Chemotherapy, business.industry, Phenylurea Compounds, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Diarrhea, Oncology, chemistry, 030220 oncology & carcinogenesis, Toxicity, Quality of Life, Geriatrics and Gerontology, medicine.symptom, business, Colorectal Neoplasms
Abstract: International audience; BACKGROUND: Regorafenib significantly increases overall survival (OS) in patients with metastatic colorectal cancer previously treated but gives toxicities. OBJECTIVES: to assess the efficacy and safety of regorafenib at it's approved dose in the older population. PATIENTS AND METHODS: This multicenter single-arm phase II enrolled patients ≥70 years old after the failure of fluoropyrimidine-based chemotherapy, anti-VEGF, and anti-EGFR treatment. The primary endpoint was disease control rate (DCR) 2 months after initiation of regorafenib (160 mg/day, 3 weeks on/1 week off). RESULTS: Forty-three patients were enrolled, with a median age of 77 years. The 2 months DCR was 31.4% in the 35 evaluable patients. For the 42 patients that received at least one dose of regorafenib, median progression-free survival and OS were 2.2 and 7.5 months. The median time to autonomy degradation and quality of life degradation was 3.1 and 3.2 months, respectively. A grade 3-4 treatment-related adverse events was observed in 35/42 patients, notably: fatigue (45.2%), hand-foot skin reaction (19.0%), hypertension (21.4%), and diarrhea (7.1%). There is a trend to achieve DCR in patients ≤80 years and a trend to discontinue the study due to toxicity in patients with ECOG ≥1, over 80 years and with impaired baseline autonomy. CONCLUSION: Treatment with regorafenib in pretreated patients ≥70 years is feasible and demonstrate similar efficacy that was observed in previous studies in young patients. Fatigue is the most frequent severe adverse event. However, caution should be taken for older patients with ECOG ≥1, over 80 years, and with impaired baseline autonomy.
Published: 2020
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13. Doxorubicin-loaded nanoparticles for patients with advanced hepatocellular carcinoma after sorafenib treatment failure (RELIVE): a phase 3 randomised controlled trial

Author: Inmaculada Ales, Hakan Harputluoglu, Marc Peeters, Jean-Marc Phelip, G. Pelletier, Zsuzsanna Kahan, Alice Gangloff, Fadi Farhat, Imam Waked, Luc Lasser, René Gerolami, Giovanni Luca, Thomas Berg, Julie Le Boulicaut, Jean-Pierre Zarski, Ivan Borbath, Wolfgang Sieghart, Ozlem Ata, Howard Ozer, Julie Vincent, Thierry Fontanges, Bartomeu Massuti, Christos Galanopoulos, Mohammed El Kassas, Audrey Molé, Imam Wakid, Philippe Merle, Nasr El Lahlouby, Andreas Maieron, Marilyne Debette-Gratien, Antonio Cubillo, György Bodoky, Sylvain Manfredi, Faiza Khemissa-Akouz, Jawad Makarem, Jean-Frédéric Blanc, Ahmet Coker, Carmen Guillén, Massimo Colombo, Michael Schultheiß, Joerg Trojan, Yann Touchefeu, Isabelle Ollivier-Hourmand, François Habersetzer, Vlad Ratziu, Amr Abdel, Amr S Saad, Miguel Marín, Magdolna Dank, Mohamed Bouattour, Hélène Regnault, Jean-Didier Grangé, Pierluigi Toniutto, Hanaa Kohail, Sameh Shamaa, Carine Richou, Erdem Goker, Eric Nguyen-Khac, Oscar Alabiso, G.-P. Pageaux, Andrea Casadei-Gardini, Moses Raj, Alexander Zipprich, Henning Wege, Ilkay Tugba, Aurore Baron, Victor Navarro, Domenico Amoroso, Issam Chehade, Nashat Gabrail, Pierre Attali, Barbara Dauvois, Stefano Tamberi, Driffa Moussata, Angela Buonadonna, Emiliano Tamburini, Muhammet Ali, Armand Abergel, Albert Tran, Suayib Yalcin, Ursula Ehmer, Hermini Manzano, Jean Delwaide, Andrés Muñoz, Carlos López, Jean-Pierre Bronowicki, Zsolt Horváth, Alper Sevinc, Gloria Sánchez, Ralph Hauke, Gabriele Luppi, Bérangère Vasseur, Nelson S. Yee, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital Charles Nicolle [Rouen]-CHU Rouen, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Service de gastro-entérologie, Merle, P., Blanc, J. -F., Phelip, J. -M., Pelletier, G., Bronowicki, J. -P., Touchefeu, Y., Pageaux, G., Gerolami, R., Habersetzer, F., Nguyen-Khac, E., Casadei-Gardini, A., Borbath, I., Tran, A., Wege, H., Saad, A. S., Colombo, M., Abergel, A., Richou, C., Waked, I., Yee, N. S., Mole, A., Attali, P., Le Boulicaut, J., Vasseur, B., Moussata, D., Grange, J. -D., Ratziu, V., Khemissa-Akouz, F., Regnault, H., Dauvois, B., Zarski, J. -P., Ollivier-Hourmand, I., Manfredi, S., Debette-Gratien, M., Gangloff, A., Fontanges, T., Baron, A., Bouattour, M., Vincent, J., Sieghart, W., Maieron, A., Peeters, M., Delwaide, J., Lasser, L., Berg, T., Schultheiss, M., Zipprich, A., Trojan, J., Ehmer, U., Luppi, G., Luca, G., Tamberi, S., Amoroso, D., Alabiso, O., Buonadonna, A., Toniutto, P., Tamburini, E., Cubillo, A., Munoz, A., Guillen, C., Sanchez, G., Manzano, H., Navarro, V., Ales, I., Massuti, B., Dank, M., Bodoky, G., Kahan, Z., Horvath, Z., Gabrail, N., Ozer, H., Galanopoulos, C., Hauke, R., Raj, M., Harputluoglu, H., Sevinc, A., Goker, E., Coker, A., Yalcin, S., Ali, M., Ata, O., Tugba, I., Elkassas, M., Abdel, A., Wakid, I., Shamaa, S., El, N., Kohail, H., Makarem, J., Chehade, I., Farhat, F., Lopez, C., and Marin, M.
Subjects: Male, Gastroenterology, law.invention, 0302 clinical medicine, Randomized controlled trial, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Clinical endpoint, Treatment Failure, ComputingMilieux_MISCELLANEOUS, education.field_of_study, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Antibiotics, Antineoplastic, Liver Neoplasms, Middle Aged, Sorafenib, 3. Good health, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 030211 gastroenterology & hepatology, Female, medicine.drug, medicine.medical_specialty, Carcinoma, Hepatocellular, Neutropenia, Population, Antineoplastic Agents, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Carcinoma, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, education, Adverse effect, Aged, Hepatology, Dose-Response Relationship, Drug, business.industry, medicine.disease, Thrombocytopenia, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Doxorubicin, Asthenia, Nanoparticles, business
Abstract: Summary Background Cytotoxic chemotherapy is generally ineffective in patients with hepatocellular carcinoma. We assessed the intravenous perfusion of doxorubicin-loaded nanoparticles in patients with hepatocellular carcinoma in whom previous sorafenib therapy had failed. Methods We did a multicentre, open-label, randomised, controlled phase 3 trial at 70 sites in 11 countries. Patients with hepatocellular carcinoma with one or more previous systemic therapies, including sorafenib, were randomly assigned to receive 30 mg/m2 doxorubicin-loaded nanoparticles (30 mg/m2 group), 20 mg/m2 doxorubicin-loaded nanoparticles (20 mg/m2 group), or standard care using a computer-generated randomisation list prepared by the funder and stratified by geographic region. Patients in the experimental groups received perfusion of the drug every 4 weeks and those in the control group received any systemic anticancer therapy (except sorafenib) as per investigator decision. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in the population of patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov , number NCT01655693 . Findings Between June 15, 2012, and Jan 27, 2017, 541 patients were screened, of whom 144 were excluded and 397 were randomly assigned to one of the groups (133 to the 30 mg/m2 group; 130 to the 20 mg/m2 group; and 134 to the control group). Median follow-up was 22·7 months (IQR 11·2–34·9). After pooling the doxorubicin groups for the efficacy analysis, median overall survival was 9·1 months (95% CI 8·1–10·4) in the pooled doxorubicin-loaded nanoparticles group and 9·0 months (7·1–11·8) in the control group (HR 1·00 [95% CI 0·78–1·28], two-sided p=0·99). 227 (94%) of 242 patients who received doxorubicin-loaded nanoparticles and 100 (75%) of 134 patients in the control group had at least one treatment-emergent adverse event. The most common drug-related grade 3 or 4 treatment-emergent adverse events were neutropenia (25 [10%] of 242 treated with doxorubicin-loaded nanoparticles and eight [6%] of 134 in the control group), asthenia (six [2%] and four [3%]), and thrombocytopenia (three [1%] and ten [7%]). Six (2%) patients treated with doxorubicin-loaded nanoparticles and one (1%) of those in the control group were deemed by investigators to have had a drug-related death. Serious adverse events occurred in 74 (31%) patients who received doxorubicin-loaded nanoparticles and 48 (36%) in the control group. Interpretation Doxorubicin-loaded nanoparticles did not improve overall survival for patients with hepatocellular carcinoma in whom previous sorafenib treatment had failed. Funding Onxeo.
Published: 2019
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14. Circulating Tumor Cells and Circulating Tumor DNA Detection in Potentially Resectable Metastatic Colorectal Cancer: A Prospective Ancillary Study to the Unicancer Prodige-14 Trial

Author: Laurent Mineur, Charles Decraene, Nicolas Kiavue, Simon Thezenas, François Ghiringhelli, Olivier Bouché, Eric Francois, Adrien Saliou, Marc-Henri Stern, Driffa Moussata, Faiza Khemissa-Akouz, Charlotte Proudhon, Marc Ychou, Thibault Mazard, Jean-Yves Pierga, François-Clément Bidard, Jordan Madic, Rosine Guimbaud, Luc Cabel, Aurore Rampanou, Michel Rivoire, Trevor Stanbury, Pascale Mariani, Institut Curie [Paris], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Compartimentation et dynamique cellulaires (CDC), Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Léon Bérard [Lyon], Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), CHU Toulouse [Toulouse], Institut Sainte Catherine [Avignon], Centre Hospitalier Saint Jean de Perpignan, Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5), R&D Unicancer [Paris], CRLCC Val d'Aurelle - Paul Lamarque, Herrada, Anthony, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Trousseau [APHP], Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP]
Subjects: 0301 basic medicine, Oncology, FOLFIRINOX, Colorectal cancer, medicine.medical_treatment, Kaplan-Meier Estimate, medicine.disease_cause, Targeted therapy, 0302 clinical medicine, Circulating tumor cell, Medicine, Digital polymerase chain reaction, Prospective Studies, Neoplasm Metastasis, lcsh:QH301-705.5, circulating tumor DNA, metastatic colorectal cancer, General Medicine, Middle Aged, Neoplastic Cells, Circulating, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, KRAS, Colorectal Neoplasms, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, circulating tumor cells, Article, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Humans, Liquid biopsy, neoplasms, Aged, Chemotherapy, liquid biopsy, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, digestive system diseases, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 030104 developmental biology, lcsh:Biology (General), Mutation, business
Abstract: The management of patients with colorectal cancer (CRC) and potentially resectable liver metastases (LM) requires quick assessment of mutational status and of response to pre-operative systemic therapy. In a prospective phase II trial (NCT01442935), we investigated the clinical validity of circulating tumor cell (CTC) and circulating tumor DNA (ctDNA) detection. CRC patients with potentially resectable LM were treated with first-line triplet or doublet chemotherapy combined with targeted therapy. CTC (Cellsearch&reg, ) and Kirsten RAt Sarcoma (KRAS) ctDNA (droplet digital polymerase chain reaction (PCR)) levels were assessed at inclusion, after 4 weeks of therapy and before LM surgery. 153 patients were enrolled. The proportion of patients with high CTC counts (&ge, 3 CTC/7.5mL) decreased during therapy: 19% (25/132) at baseline, 3% (3/108) at week 4 and 0/57 before surgery. ctDNA detection sensitivity at baseline was 91% (N=42/46) and also decreased during treatment. Interestingly, persistently detectable KRAS ctDNA (p = 0.01) at 4 weeks was associated with a lower R0/R1 LM resection rate. Among patients who had a R0/R1 LM resection, those with detectable ctDNA levels before liver surgery had a shorter overall survival (p &lt, 0.001). In CRC patients with limited metastatic spread, ctDNA could be used as liquid biopsy tool. Therefore, ctDNA detection could help to select patients eligible for LM resection.
Published: 2019
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15. Modified FOLFIRINOX Versus CISGEM Chemotherapy for Patients With Advanced Biliary Tract Cancer (PRODIGE 38 AMEBICA): A Randomized Phase II Study.

Author: Phelip, Jean Marc, Desrame, Jérôme, Edeline, Julien, Barbier, Emilie, Terrebonne, Eric, Michel, Pierre, Perrier, Hervé, Dahan, Laetitia, Bourgeois, Vincent, Akouz, Faiza Khemissa, Soularue, Emilie, Ly, Valérie Lebrun, Molin, Yann, Lecomte, Thierry, Ghiringhelli, François, Coriat, Romain, Louafi, Samy, Neuzillet, Cindy, Manfredi, Sylvain, and Malka, David
Published: 2022
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16. A phase III study evaluating oral glutamine and transforming growth factor-beta 2 on chemotherapy-induced toxicity in patients with digestive neoplasm

Author: Isabelle Cristiani, Laurent Mineur, Julie Courraud, Eric Assenat, Fideline Collin, Hélène de Forges, Pierre Senesse, Caroline Amsellem, C. Janiszewski, Pierre Déchelotte, Faiza Khemissa, Mohamed Ramdani, Patrick Bachmann, Centre Hospitalier Saint Jean de Perpignan, Institut Sainte Catherine [Avignon], Service de nutrition [CHU Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier de Béziers, Centre Léon Bérard [Lyon], Nestlé Research Center, Nestlé Suisse, Dynamique des capacités humaines et des conduites de santé (EPSYLON), and Université de Montpellier (UM)-Université Paul-Valéry - Montpellier 3 (UPVM)-Université Montpellier 1 (UM1)
Subjects: Male, medicine.medical_specialty, Cachexia, Gastrointestinal Diseases, Glutamine, medicine.medical_treatment, Platinum Compounds, Bioinformatics, Gastroenterology, law.invention, Immunonutrition, Gastrointestinal cancer, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, Transforming Growth Factor beta, law, Internal medicine, Multicenter trial, Antineoplastic Combined Chemotherapy Protocols, medicine, Chemotherapy, Humans, Side effects, Aged, Gastrointestinal Neoplasms, Hepatology, business.industry, Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Middle Aged, medicine.disease, 3. Good health, Digestive neoplasm, 030220 oncology & carcinogenesis, Dietary Supplements, Female, 030211 gastroenterology & hepatology, Fluorouracil, business
Abstract: Background Patients with gastrointestinal (GI) cancer are exposed to cachexia, which is highly correlated with chemotherapy-induced side effects. Research suggests that specific immunonutrients could prevent such toxicities. Aims The primary objective of this phase III study was to evaluate the efficacy of glutamine and transforming growth factor-β2 (TGF-β2) in the prevention of grade 3–4 non-hematological toxicities induced by chemotherapy in patients with GI cancer. Patients and methods We designed a double-blind, randomized, controlled and multicenter trial stratified according to center, type of chemotherapy, presence of cachexia, and age. Patients were randomized to receive either Clinutren Protect® (CP) or a control isocaloric diet (without TGF-β2 or glutamine). Results Between November 2007 and October 2011, 210 patients were enrolled in the study, of which 201 were included in the intention-to-treat analysis. Grade 3–4 non-hematological toxicities were not significantly different between the CP and control groups when evaluated by univariate and multivariate analyses. Likewise, no difference was observed regarding grade 3–4 hematological toxicities or reasons for treatment interruption. Conclusion This randomized study does not support the hypothesis that oral glutamine and TGF-β2 supplementation is effective to reduce grade 3 or 4 non-hematological toxicities induced by chemotherapy in patients with GI neoplasm.
Published: 2016
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17. FOLFIRINOX as induction treatment in rectal cancer patients with synchronous metastases: Results of the FFCD 1102 phase II trial

Author: Laetitia Dahan, J.P. Lagasse, P.L. Etienne, Julien Taieb, C.-B. Levaché, Emilie Barbier, J. Thaury, A. Bedjaoui, C. Desauw, Simon Pernot, Jean-Luc Raoul, Olivier Lucidarme, Olivier Dupuis, Dominique Auby, F. Di Fiore, François Ghiringhelli, M. Baconnier, Faiza Khemissa, J-B. Bachet, Gilles Breysacher, Albert Aleba, Côme Lepage, Thierry Lecomte, S. Nguyen, Fabien Brocard, Eric Terrebonne, Service d'oncologie médicale [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de Radiologie [CHU Pitié-Salpétrière], Oncologie digestive [Clinique Francheville, Périgueux], Clinique Francheville [Périgueux], Université Bourgogne Franche-Comté [COMUE] (UBFC), Equipe EPICAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], CHU Trousseau [APHP]-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service d'oncologie médicale (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Oncologie médicale [Polyclinique de Gentilly, Nancy], Polyclinique de Gentilly, Université Sorbonne Paris Cité (USPC), Université Paris Descartes - Paris 5 (UPD5), Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'hépato-gastro-entérologie et oncologie digestive [CHR Orléans], Centre Hospitalier Régional d'Orléans (CHR), Département d'oncologie médicale [Rouen], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Clinique Armoricaine de Radiologie [St. Brieuc], Oncologie digestive [CH General Niort], CH Niort, Service d'Oncologie médicale [Clinique Victor Hugo], Clinique Victor Hugo, Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Hépato-gastro-entérologie et endoscopies digestives [ [Hôpital Européen Georges Pompidou], Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre hospitalier de Pau, CH Annecy, Service d'Oncologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Régional d'Orléans (CHRO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP]
Subjects: Male, Cancer Research, Lung Neoplasms, Colorectal cancer, FOLFIRINOX, Gastrointestinal Diseases, Synchronous metastases, Leucovorin, Kaplan-Meier Estimate, Induction, 0302 clinical medicine, Induction therapy, Antineoplastic Combined Chemotherapy Protocols, Rectal cancer, INDUCTION TREATMENT, Fatigue, Response rate (survey), medicine.diagnostic_test, Liver Neoplasms, Remission Induction, Middle Aged, Combined Modality Therapy, Magnetic Resonance Imaging, Progression-Free Survival, 3. Good health, Oxaliplatin, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Radiology, Fluorouracil, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma, Irinotecan, 03 medical and health sciences, medicine, Humans, Paresthesia, Aged, Performance status, business.industry, Rectal Neoplasms, Magnetic resonance imaging, medicine.disease, Hematologic Diseases, Confidence interval, Local control, business, Tomography, X-Ray Computed, Follow-Up Studies
Abstract: Aim of the study The optimal therapeutic strategy in patients with rectal cancer and synchronous unresectable metastases remains unknown. We evaluated the efficacy of FOLFIRINOX induction therapy in this setting. Patients and methods Chemotherapy-naive patients received at least 8 cycles of FOLFIRINOX. The primary end-point was the 4-month disease control (4 m DC) rate. Tumour responses were centrally reviewed and assessed by computed tomography scan for metastases (Response Evaluation Criteria in Solid Tumours criteria) and magnetic resonance imaging for rectal tumorus. With a Simon 2-stage design and a targeted (H1) 4 m DC > 75%, 65 patients were enrolled from July 2012 to February 2015: male, 78%; median age, 61 years; performance status, 0–1, 98%; liver metastases, 92%; ≥2 metastatic sites, 63%. Results Fifty-six (85%) of the 65 patients received the 8 planned FOLFIRINOX cycles. The primary objective was achieved (4 m DC rate: 94%; 95% confidence interval [CI], 86.3–97.8). Primary tumour symptoms decreased from 72% at baseline to 10% at 4 months. Response rate was 86%, and a >70% primary tumour volume decrease was seen in 63% of patients. Forty-four patients (68%) had at least one grade 3 side-effect; no toxic deaths occurred. Median follow-up was 35.0 months (95% CI, 31.3–43.7). Median progression-free survival and overall survival were 10.9 m (95% CI, 8.8–12.9) and 33.4 m (95% CI, 22.6–38.2), respectively. Conclusion Upfront FOLFIRINOX is feasible and allows good local and distant control. It therefore offers the opportunity to choose the best therapeutic strategy for each patient and to personalise treatment according to the local and distant efficacy results of this induction step. Trial registration Clinicaltrials.gov, NCT01674309 .
Published: 2018
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18. Pravastatin combination with sorafenib does not improve survival in advanced hepatocellular carcinoma

Author: Jean-Pierre Bronowicki, Jean-Louis Legoux, Thierry Lecomte, Jean-François Seitz, Olivier Bouché, Sylvain Manfredi, Prodige Investigators, Emilie Barbier, Jean-Marc Phelip, Eric Nguyen Khac, Ghassan Riachi, Isabelle Ollivier-Hourmand, Jacques Denis, Jean-Louis Jouve, Julien Vergniol, Anne-Laure Villing, Maryline Debette-Gratien, Jean-François Ramée, Roger Faroux, and Faiza Khemissa Akouz
Subjects: 0301 basic medicine, Oncology, Sorafenib, Adult, Diarrhea, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Antineoplastic Agents, Kaplan-Meier Estimate, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, neoplasms, Aged, Pravastatin, Aged, 80 and over, Univariate analysis, Hepatology, Performance status, business.industry, Liver Neoplasms, Middle Aged, medicine.disease, Prognosis, digestive system diseases, Progression-Free Survival, Clinical trial, 030104 developmental biology, Hepatocellular carcinoma, Quality of Life, 030211 gastroenterology & hepatology, Female, business, Liver cancer, medicine.drug, Follow-Up Studies
Abstract: Background & Aims Sorafenib is the standard of care for advanced hepatocellular carcinoma (HCC). Combining sorafenib with another treatment, to improve overall survival (OS) within an acceptable safety profile, might be the next step forward in the management of patients with advanced HCC. We aimed to assess whether a combination of sorafenib and a statin improved survival in patients with HCC. Methods The objective of the PRODIGE-11 trial was to compare the respective clinical outcomes of the sorafenib-pravastatin combination (arm A) versus sorafenib alone (arm B) in patients with advanced HCC. Child-Pugh A patients with advanced HCC who were naive to systemic treatment (n = 323) were randomly assigned to sorafenib-pravastatin combination (n = 162) or sorafenib alone (n = 161). The primary endpoint was OS; secondary endpoints were progression-free survival, time to tumor progression, time to treatment failure, safety, and quality of life. Results After randomization, 312 patients received at least 1 dose of study treatment. After a median follow-up of 35 months, 269 patients died (arm A: 135; arm B: 134) with no difference in median OS between treatments arms (10.7 months vs. 10.5 months; hazard ratio = 1.00; p = 0.975); no difference was observed in secondary survival endpoints either. In the univariate analysis, the significant prognostic factors for OS were CLIP score, performance status, and quality of life scores. The multivariate analysis showed that the only prognostic factor for OS was the CLIP score. The main toxicity was diarrhea (which was severe in 11% of patients in arm A, and 8.9% in arm B), while severe nausea-vomiting was rare, and no toxicity-related deaths were reported. Conclusion Adding pravastatin to sorafenib did not improve survival in patients with advanced HCC. Lay summary Sorafenib has proven efficacy for the treatment of patients with advanced hepatocellular carcinoma. However, overall survival remains poor in these patients, so we were interested to see if the addition of a statin, pravastatin, improved outcomes in patients with advanced HCC. This randomized-controlled trial demonstrated that the sorafenib-pravastatin combination did not improve overall survival in this study population compared to sorafenib alone. Clinical trial number: NCT01075555.
Published: 2018

19. Overweight is associated to a better prognosis in metastatic colorectal cancer: A pooled analysis of FFCD trials

Author: Mireille Mousseau, Eric Francois, A. Fatisse, A. Bedjaoui, Abakar Mahamat, C. Lombard-Bohas, J. Ezenfis, Marc Porneuf, F. Subtil, M. Tissot, Emilie Maillard, M. Fayolle, J.F. Dor, A. Votte, P. Chiappa, P. Prost, Denis Cléau, P. Bergerault, J.C. Souquet, K. Beerblock, P. Chatrenet, J.M. Sabate, M. Carreiro, S. Beorchia, Vincent Hautefeuille, Jessika Moreau, N. Delas, C. Vilain, Christian Borel, Franck Audemar, M. Duluc, Touraj Mansourbakht, Bernard Denis, Gael Deplanque, Jean-Marc Phelip, C. Brezault, Anne Thirot-Bidault, L. Gasnault, Jean-Louis Jouve, Y. Rinaldi, B. Leduc, Y. Courouble, A. Alessio, Matthieu Schnee, P. Cassan, Antoine Adenis, Jocelyne Provencal, A. Botton, Laurent Cany, Françoise Desseigne, Marie-Christine Kaminsky, Mohamed Ramdani, B. Lafforgue, L. Rob, J.C. Barbare, S. Jacquot, A. Zaanan, J.-Y. Douillard, C. Cornila, B. Rhein, Benjamin Linot, Z. Ladhib, D. Zylberait, Cedric Lecaille, N. Hess-Laurens, H. Brixi-Benmansour, C. Rebischung, C. Giraud, L. Stefani, D. Pillon, J.P. Lafargue, J. Forestier, P. Laplaige, C. Paoletti, S. Lavau Denes, Etienne Suc, A. Patenotte, E. Echinard, François-Xavier Caroli-Bosc, D. Goldfain, V. Quentin, Hervé Perrier, J.D. Grangé, A. Marre, M. Baconnier, Bruno Coudert, Thomas Walter, R. Benoit, A. Blanchi, A.C. Dupont-Gossart, Emilie Barbier, X. Coulaud, D. Besson, Isabelle Trouilloud, D. Sevin-Robiche, M Giovannini, O. Boulat, C. Lobry, H. Castanie, Y. Molin, Thomas Aparicio, Valérie Boige, P. Lehair, J.P. Robin, J.P. Latrive, J. Goineau, Clément Belletier, G. Medinger, C. Lepere, Philippe Rougier, N. Bouaria, E. Carola, V. Derias, Bernard Paillot, Yves Becouarn, F. Kikolski, Martin Combe, Julie Vincent, C. Briac-Levaché, C. Becht, François Ghiringhelli, J. Charneau, Dany Gargot, Julien Vergniol, Denis Péré-Vergé, P. Pienkowski, Patrick Texereau, I. Baumgaertner, J.P. Ramain, Pierre-Luc Etienne, P. Claudé, Jean Francois Paitel, J.P. Plachot, M.-C. Clavero-Fabri, P. Geoffroy, A. Cadier-Lagnes, Y. Le Bricquir, S. Fratte, O. Favre, Aimery de Gramont, J. Butel, David Tougeron, B. Winkfield, E. Janssen, J. Meunier, Julien Volet, N. Gérardin, D. Soubrane, Vincent Bourgeois, Xavier Adhoute, Y.H. Lam, P.A. Haineaux, A. Rotenberg, J-B. Bachet, C. Berger, F. Almaric, J. Tuaillon, G. Gatineau-Saillant, F. Zerouala-Boussaha, E. Cuillerier, R. Lamy, D. Luet, D. Baudet-Klepping, E.A. Pariente, M. Gignoux, J. Martin, M. Blasquez, Romain Coriat, C. Bineau, J. Boutin, A. Aouakli, F. Dewaele, A.M. Queuniet, V. Sebbagh, P. Couzigou, N. Barrière, Faiza Khemissa, P. Follana, Laurence Chone, F. Petit-Laurent, N. Abdelli, Olivier Capitain, D. Bechade, Corinne Sarda, J.P. Herr, P. Pouderoux, Julien Taieb, M. Pauwels, E. Zrihen, L. Wander, Gael Goujon, G. Boilleau-Jolimoy, Anne Thirot Bidault, B. Landi, V. Jestin Le Tallec, Jaafar Bennouna, O. Berthelet, M. Glikmanas, H. Salloum, Côme Lepage, Thierry Lecomte, P. Amoyal, C. Platini, Veronique Guerin-Meyer, B. Garcia, Laetitia Dahan, Pascal Burtin, J. Villand, S. Nguyen, A. Roussel, F. Di Fiore, S. Oddou-Lagraniere, J.P. Aucouturier, Veronique Lorgis, Gerard Cavaglione, J.P. Lagasse, Dominique Auby, Pierre Michel, F. Bonnetain, Gilles Breysacher, R. Mackiewicz, Philippe Ruszniewski, T. Morin, J. Thaury, Clara Locher, J.M. Vantelon, S. Nasca, J.P. Barbieux, H. Maechel, Y. Coscas, May Mabro, S. Montembault, P. Novello, M. Charbit, J. Deguiral, A. Gagnaire, D. Festin, A. Gueye, Hélène Senellart, Achim Weber, Nadia Bouarioua, Jérôme Dauba, Michel Ducreux, Jean-Luc Raoul, G. Coulanjon, J.N. Vaillant, S. Chaussade, A. Gilbert, Anne-Laure Villing, Dominique Genet, P. Martin, M. Ben Abdelghani, M.P. Galais, A. Azzedine, A. Lemaire, C. Barberis, C. Buffet, J. Egreteau, G. Roquin, M. Mornet, Isabelle Cumin, M. Pelletier, P. Feydy, J. Lacourt, T. Chatellier, Jean-Louis Legoux, M. Benchalal, I. Graber, S. Nahon, P. Pantioni, A. Hollebecque, M. Zawadi, Pascal Hammel, M. Mignot, Roger Faroux, J. Lafon, Mohamed Gasmi, Jean-Philippe Spano, S. Pesque-Penaud, C. de la Fouchardiere, J. Cretin, Olivier Bouché, D. Smith, E. Norguet-Monnereau, G. Bordes, Sylvain Manfredi, Thévenet P, Herve Lacroix, E. Dorval Danquechin, Eric Terrebonne, Laurent Bedenne, P. Godeau, David Malka, V. Veuillez, Emmanuel Mitry, F. Riot, Sandrine Hiret, François Morvan, M.C. Gouttebel, Jean-François Seitz, Karine Bouhier-Leporrier, N. Stremsdoerfer, P. Souillac, M. Mozer, C. Couffon, F. Husseini, J.M. Cheula, J.-M. Gornet, K. Slimane Fawzi, Service d'hépato-gastro-entérologie [Hôpital Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Université Paris-Saclay, Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de gastroentérologie (CHD Vendee - Hopital Les Oudairies, La Roche Sur Yon), CHD Vendee (La Roche Sur Yon), Fédération Francophone de la Cancérologie Digestive, FFCD, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Privé des Côtes d'Armor (HPCA), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Institut de Cancérologie de la Loire [Saint-Priest en Jarez], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Service d'hépato-gastro-entérologie et oncologie digestive [CHR Orléans], Centre Hospitalier Régional d'Orléans (CHRO), Service De Gastroenterologie, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Hôpital Louis Pasteur [Colmar] (CH Colmar), Département d'hépato-gastro-entérologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut des Maladies de l’Appareil Digestif [CHU Nantes], Service d'oncologie [Institut Hospitalier Franco-Britannique : Levallois-Perret], Institut hospitalier Franco-Britannique [Levallois-Perret], Département d'oncologie médicale (CHU Robert Debré, Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Hôpital Charles Nicolle [Rouen]-CHU Rouen, and Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN)
Subjects: Male, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Bevacizumab, Colorectal cancer, Angiogenesis Inhibitors, [SDV.CAN]Life Sciences [q-bio]/Cancer, Kaplan-Meier Estimate, Overweight, Gastroenterology, Pooled analysis, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Outcome Assessment, Health Care, Individual data, medicine, Overall survival, Humans, Neoplasm Metastasis, Objective response, Aged, 2. Zero hunger, Clinical Trials as Topic, Prognostic factor, business.industry, nutritional and metabolic diseases, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Prognosis, medicine.disease, 3. Good health, 030104 developmental biology, Oncology, Normal weight, 030220 oncology & carcinogenesis, Female, medicine.symptom, Colorectal Neoplasms, business, medicine.drug
Abstract: IF 7.191 (2017); International audience; BACKGROUND:Previous studies showed that high and low body mass index (BMI) was associated with worse prognosis in early-stage colorectal cancer (CRC), and low BMI was associated with worse prognosis in metastatic CRC (mCRC). We aimed to assess efficacy outcomes according to BMI.PATIENTS AND METHODS:A pooled analysis of individual data from 2085 patients enrolled in eight FFCD first-line mCRC trials from 1991 to 2013 was performed. Comparisons were made according to the BMI cut-off: Obese (BMI ≥30), overweight patients (BMI ≥ 25), normal BMI patients (BMI: 18.5-24) and thin patients (BMI
Published: 2018
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20. Bevacizumab Maintenance Versus No Maintenance During Chemotherapy-Free Intervals in Metastatic Colorectal Cancer: A Randomized Phase III Trial (PRODIGE 9)

Author: Stephane Jacquot, Karine Le Malicot, Christian Borel, Julien Taieb, Valérie Boige, Thomas Aparicio, Jean-Marc Phelip, Dominique Genet, Jaafar Bennouna, Laetitia Dahan, Roger Faroux, Etienne Suc, Faiza Khemissa, E. Francois, Côme Lepage, Prodige Investigators, François Ghiringhelli, Patrick Texereau, Françoise Desseigne, Olivier Bouché, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Service de Médecine Nucléaire, Centre Georges-François Leclerc [Dijon] (CGFL), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Institut Gustave Roussy (IGR), Fédération Francophone de la Cancérologie Digestive, FFCD, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER, CRLCC Paul Strauss, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Polyclinique de Limoges - Site Émailleurs-Colombier [Limoges], Centre Hospitalier Saint Jean de Perpignan, Clinique Saint-Jean Languedoc [Toulouse] (CSJL), Centre Léon Bérard [Lyon], CHU Mont de Marsan, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, université de Bourgogne, LNC, UNICANCER-Université Côte d'Azur (UCA), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), CHU Saint Louis [APHP], Université Sorbonne Paris Cité ( USPC ), Service de Médecine Nucléaire, Centre Georges-François Leclerc [Dijon] ( CGFL ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Institut Gustave Roussy ( IGR ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), CRLCC Antoine Lacassagne, Hôpital de la Timone [CHU - APHM] ( TIMONE ), Institut de recherche en cancérologie de Montpellier ( IRCM ), Université Montpellier 1 ( UM1 ) -CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Clinique Saint Jean Languedoc, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Institut de Cancérologie de l'Ouest
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, medicine.medical_specialty, Time Factors, Bevacizumab, Colorectal cancer, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, law.invention, 03 medical and health sciences, 0302 clinical medicine, Antineoplastic Agents, Immunological, [SDV.CAN] Life Sciences [q-bio]/Cancer, Randomized controlled trial, law, Internal medicine, medicine, Humans, Neoplasm Metastasis, Aged, Chemotherapy, business.industry, Induction chemotherapy, Induction Chemotherapy, Middle Aged, medicine.disease, 3. Good health, Irinotecan, Regimen, 030104 developmental biology, Fluorouracil, 030220 oncology & carcinogenesis, Female, business, Colorectal Neoplasms, Metastatic Colorectal Cancer, medicine.drug
Abstract: Purpose Conflicting results are reported for maintenance treatment with bevacizumab during chemotherapy-free intervals (CFI) in metastatic colorectal cancer after induction chemotherapy. Patients and Methods In this open-label, phase III, randomized controlled trial, we compared the tumor control duration (TCD) observed with bevacizumab maintenance and with no treatment (observation) during CFI subsequent to induction chemotherapy with 12 cycles of fluorouracil, leucovorin, and irinotecan plus bevacizumab. After disease progression, the induction regimen was repeated for eight cycles, followed by a new CFI. Results From March 2010 to July 2013, 491 patients were randomly assigned. Disease progression or death occurred during induction chemotherapy in 85 patients (17%); 261 patients (53%) had at least one reinduction, 107 (22%) had two reinductions, and 56 (11%) had three or more reinductions. The median TCD was 15 months in both groups; the median progression-free survival (PFS) from randomization was 9.2 and 8.9 months in the maintenance group and observation groups, respectively. The TCD observed in both groups was higher compared with the TCD hypotheses of the trial. The median overall survival (OS) was 21.7 and 22.0 months in the maintenance and observation groups, respectively. In the per-protocol population, defined as patients with at least one reinduction after the first progression, the median duration of the first CFI was 4.3 months in both arms; the median TCD was 17.8 and 23.3 months ( P = .339), the median PFS was 9.9 and 9.5 months, and the median OS was 27.6 and 28.5 months in the maintenance and observation groups, respectively. Multivariable analysis revealed that female gender, WHO performance status ≥ 2, and unresected primary tumors were associated with a shorter TCD. Conclusion Bevacizumab maintenance monotherapy did not improve TCD, CFI duration, PFS, or OS.
Published: 2018
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21. Regorafenib combined with irinotecan as second-line treatment in patients with metastatic gastro-oesophageal adenocarcinomas: A randomized phase 2 trial (PRODIGE 58 – UCGI 35 – REGIRI)

Author: C. de la Fouchardiere, Sophie Gourgou, Laetitia Dahan, Marine Gilabert, M. Benabdelghani, David Sefrioui, Anthony Turpin, L. Monard, A. Hennequin, Hélène Senellart, A. Lopez, Emmanuelle Samalin, A. Zaanan, Faiza Khemissa, Ludovic Evesque, and O. Bouche
Subjects: medicine.medical_specialty, Second line treatment, business.industry, Hematology, medicine.disease, Gastroenterology, Irinotecan, chemistry.chemical_compound, Oncology, chemistry, Gastro, Regorafenib, Internal medicine, medicine, Adenocarcinoma, In patient, business, medicine.drug
Published: 2019
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22. Geriatric factors analyses from FFCD 2001-02 phase III study of first-line chemotherapy for elderly metastatic colorectal cancer patients

Author: Faiza Khemissa, Jean-François Seitz, J. Cretin, Olivier Bouché, Laurent Teillet, Dominique Genet, Jean-Baptiste Bachet, Jean-Louis Jouve, Olivier Boulat, Dany Gargot, Thierry Lecomte, Céline Lepère, Mohamed Ramdani, Gilles Breysacher, Christophe Locher, Iradj Sobhani, Emilie Maillard, Emmanuel Mitry, Thomas Aparicio, Dominique Auby, Roger Faroux, Mohamed Gasmi, Laetitia Stefani, Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fédération Francophone de la Cancérologie Digestive, FFCD, CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpitaux Civils Colmar, Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Image et ville (IV), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Département de cancérologie et d'hématologie, CHU Grenoble-Hôpital Michallon, Service Hépato-gastroentérologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Département de Médecine, Centre Hospitalier Libourne, Centre Hospitalier Départemental Les Oudairies, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de gastro-entérologie [Henri Mondor AP-HP, Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Institut Curie [Paris], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre hospitalier de Libourne, Service de gastroentérologie et cancérologie digestive [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de gastro-entérologie - Hôpital Henri Mondor, Institut Curie, Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Image et ville ( IV ), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Institut d'Electronique et de Télécommunications de Rennes ( IETR ), Université de Nantes ( UN ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire de Tours ( CHRU TOURS ), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique ( MEPPOT - U1147 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Oncology, Male, Cancer Research, medicine.medical_specialty, Multivariate analysis, Colorectal cancer, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Kaplan-Meier Estimate, Prognostic factors, Irinotecan, Disease-Free Survival, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Carcinoembryonic antigen, Elderly, Quality of life, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Karnofsky Performance Status, Neoplasm Metastasis, Prospective cohort study, Geriatric Assessment, Aged, Aged, 80 and over, Chemotherapy, biology, business.industry, medicine.disease, 3. Good health, Treatment Outcome, Fluorouracil, 030220 oncology & carcinogenesis, biology.protein, Quality of Life, Camptothecin, Female, business, Colorectal Neoplasms, medicine.drug
Abstract: IF 6.163; International audience; AIM:Several predictors of metastatic colorectal cancer (mCRC) outcomes have been described. Specific geriatric characteristics could be of interest to determine prognosis.METHOD:Elderly patients (75+) with previously untreated mCRC were randomly assigned to receive infusional 5-fluorouracil-based chemotherapy, either alone (FU) or in combination with irinotecan (IRI). Geriatric evaluations were included as an optional procedure. The predictive value of geriatric parameters was determined for the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS).RESULTS:From June 2003 to May 2010, the FFCD 2001-02 randomised trial enrolled 282 patients. A baseline geriatric evaluation was done in 123 patients; 62 allocated to the FU arm and 61 to the IRI arm. The baseline Charlson index was ≤1 in 75%, Mini-Mental State Examination was ≤27/30 in 31%, Geriatric Depression Scale was >2 in 10% and Instrumental Activities of Daily Living (IADL) was impaired in 34% of the patients. Multivariate analyses revealed that no geriatric parameter was predictive for ORR or PFS. Normal IADL was independently associated with better OS. The benefit of doublet chemotherapy on PFS differed in subgroups of patients ≤80 years, with unresected primary tumour, leucocytes >11,000 mm3 and carcinoembryonic antigen >2N. There was a trend towards better OS in patients with normal IADL.CONCLUSION:The autonomy score was an independent predictor for OS. A trend toward a better efficacy of doublet chemotherapy in some subgroups of patients was reported and should be further explored.
Published: 2016
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23. Malnutrition in Patients With Cancer: Comparison of Perceptions by Patients, Relatives, and Physicians-Results of the NutriCancer2012 Study

Author: Bruno Raynard, Sandrine Oziel-Taieb, Marie Lespiau Movschin, Jean-Philippe Durand, Christophe Hebert, Xavier Hébuterne, Sebastien Gouy, Francesco Savinelli, Nicolas Flori, Cécile Bannier Braticevic, Emmanuel Gyan, François Goldwasser, Jean Lacau Saint Guily, Faiza Khemissa, and Gilbert Zeanandin
Subjects: 0301 basic medicine, Adult, Pediatrics, medicine.medical_specialty, Adolescent, Medicine (miscellaneous), Nutritional Status, Comorbidity, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Quality of life, Weight loss, Neoplasms, Physicians, Surveys and Questionnaires, medicine, Prevalence, Humans, In patient, Family, Aged, Aged, 80 and over, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, Malnutrition, Cancer, Middle Aged, medicine.disease, Closest relatives, Cross-Sectional Studies, 030220 oncology & carcinogenesis, Female, medicine.symptom, business, Body mass index, Attitude to Health
Abstract: Malnutrition is a critical predictor of toxicity and outcome in patients with cancer and may be perceived differently by patients, relatives, and physicians.To assess the prevalence of malnutrition in oncology departments and to compare it with the perceptions of nutrition status by patients themselves, their closest relatives, and attending physicians.A 1-day multicentric cross-sectional survey on the prevalence of malnutrition was conducted in different oncology departments using patient-, relative-, and physician-specific questionnaires. Malnutrition was defined by a weight loss ≥5% within 1 month or ≥10% within 6 months, a body mass index ≤18.5 kg/mA total of 2197 patients were included, and 2071 and 976 questionnaires were collected from patients and relatives, respectively. Prevalence of malnutrition was 39%. Physicians overestimated malnutrition (44%), whereas patients and relatives underestimated it (22% and 23%, respectively, P.001). Conversely, malnutrition-associated symptoms were underestimated by physicians compared with patients and relatives.We found a prevalence of malnutrition of 39%: it was underestimated by patients and relatives and overestimated by physicians.
Published: 2016

24. Impact d’une prise en charge diététique précoce et active sur les toxicités de grade 3 ou plus chez des patients en première ligne de chimiothérapie pour cancer colorectal métastatique

Author: A. Abakar Mahamat, Faiza Khemissa, Thibault Mazard, J.F. Seitz, Eric Francois, Patrick Bachmann, Xavier Hébuterne, L. Mineur, Isabelle Besnard, Stéphane M. Schneider, and Pierre Senesse
Subjects: Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine
Abstract: Introduction et but de l’etude Chez les malades atteints de cancer, la denutrition induit une perte de chance. Le but de ce travail etait d’evaluer le benefice d’une prise en charge dietetique precoce et active chez des patients en premiere ligne de chimiotherapie pour cancer colorectal (CCR) metastatique. Materiel et methodes Dans une etude prospective, multicentrique, des patients non denutris ont ete randomises pour beneficier (G1) ou non (G2) d’une prise en charge dietetique precoce et active. Les patients du G1 recevaient des conseils nutritionnels par un dieteticien au debut du traitement, puis tous les 15j ; ceux du G2 avaient une prise en charge standard. Dans les deux groupes, des complements nutritionnels oraux (CNO) ou une nutrition artificielle (NA) etaient prescrits selon les recommandations. L’objectif principal etait d’evaluer la survenue de toxicite grade 3 ou plus au cours du suivi de 1 an. Pour mettre en evidence une difference de 20 % entre les deux groupes avec une puissance de 80 % au risque α = 0,05, le nombre de sujets necessaires etait de 80 par groupe. Les analyses ont ete realisees par regression logistique ou test du Chi2. Une difference etait significative pour p Resultats et analyse statistique Cent soixante-treize patients ont ete evalues en ITT : G1 (n = 85, F/H : 31/54, 64 ± 13 ans) ; G2 (n = 88, F/H : 34/54 ; 63 ± 12 ans). Le nombre de sites metastatiques, le performance status (PS 0/1/2 : 47/38/0 vs 44/41/3) et l’IMC a l’inclusion (24,9 ± 3,6 vs 26,3 ± 4,0) etaient identiques. Les chimiotherapies (FOLFIRI 50,6 vs 52,3 %, FOLFOX 30,6 vs 29,5 %, FOLFIRINOX 11,8 vs 10,2 % ou 5 FU seul 7,0 vs 8,0 %) etaient identiques dans G1 et G2. Une therapie ciblee etait associee chez 63,5 et 71,6 % des malades. Une toxicite de grade 3 ou plus etait observee chez 49,4 % des patients du G1 et 67 % du G2 (RR = 0,367 ; IC 95 % : 0,186–0,722 ; p = 0,0037). Le delai median de survenue de la toxicite etait de 359j (182–…) vs 169j (118–252). 9,4 % des patients du G1 et 19,3 % du G2 sont decedes (p = 0,065). Les apports energetiques et proteiques des patients du G1 etaient superieurs de 222 ± 76 kcal/j et 11,4 ± 4,8 g/j a ceux du G2 (p = 0,004). Les variations de poids etaient en faveur du G1 (p = 0,007) ; a M3 les patients du G1 avaient un poids stable et ceux du G2 avaient perdu −1,2 ± 0,6 kg. A M6, 14,8 % des patients du G1 et 30,8 % des patients du G2 (p = 0,03) etaient denutris ; 41,4 % des patients du G1 et 26,9 % de ceux du G2 (p = 0,087) avaient un PS 0. Des CNO ont ete prescrits chez 48,2 % du G1 et 61,4 % du G2 (p = 0,08) et une NA chez 7,1 % du G1 et 14,8 % du G2 (p = 0,105). Conclusion Cette etude demontre qu’une prise en charge dietetique precoce et active reduit le risque de developper une toxicite de grade 3 et plus chez des malades en premiere ligne de chimiotherapie pour CCR metastatique. Meme si une extrapolation des resultats a d’autres situations reste a demontrer, ce travail plaide pour une systematisation de la prise en charge dietetique chez les malades traites par chimiotherapie.
Published: 2018
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25. Phase II trial to evaluate efficacy and tolerance of regorafenib monotherapy in patients (pts) over 70 with previously treated metastatic colorectal adenocarcinoma (mCRC) FFCD 1404 - REGOLD

Author: M. Ben Abdelghani, G. Des Guetz, Eric Assenat, C. Le Foll, Olivier Romano, Jean-Louis Legoux, Côme Lepage, L. Cany, M. Dhooge, Catherine Delbaldo, A. Darut Jouve, Thomas Aparicio, Denis Smith, M. Duluc, Claire Falandry, Faiza Khemissa, Yves Rinaldi, Pascal Artru, Carole Monterymard, and Bruno Valenza
Subjects: Brachial Plexus Neuritis, medicine.medical_specialty, business.industry, Phases of clinical research, Hematology, Gastroenterology, 03 medical and health sciences, Large Intestine Adenocarcinoma, chemistry.chemical_compound, 0302 clinical medicine, Oncology, chemistry, 030220 oncology & carcinogenesis, Internal medicine, Regorafenib, medicine, 030211 gastroenterology & hepatology, Colorectal adenocarcinoma, In patient, Previously treated, business
Published: 2018
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26. Induction chemotherapy (CT) with FOLFIRINOX or FOLFOX/FOLFIRI, plus cetuximab (CET) or bevacizumab (BEV) (by RAS status), in patients (pts) with primarily unresectable colorectal liver metastases (CRLM): Results of the randomized UNICANCER PRODIGE 14-ACCORD 21 (METHEP-2) trial

Author: Claire Jouffroy-Zeller, Marie Pierre Galais, Philippe Houyau, François Ghiringhelli, Marc Ychou, Anne Mercier Blas, René Adam, Thomas Aparicio, Laurent Mineur, Eric Assenat, Rosine Guimbaud, Antoine Adenis, Marion Chauvenet, Olivier Bouché, Faiza Khemissa, Simon Thezenas, Michel Rivoire, Eric Francois, Yves Becouarn, and Franck Audemar
Subjects: Oncology, Liver surgery, Cancer Research, medicine.medical_specialty, Cetuximab, Bevacizumab, business.industry, FOLFIRINOX, Induction chemotherapy, 03 medical and health sciences, 0302 clinical medicine, FOLFOX, 030220 oncology & carcinogenesis, Internal medicine, medicine, FOLFIRI, 030211 gastroenterology & hepatology, In patient, business, medicine.drug
Abstract: 3535Background: pts with unresectable CRLM who respond to induction CT allowing curative-intent liver surgery have longer overall survival (OS) than pts who do not. Triplet (3-) or doublets (2-) CT...
Published: 2018
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27. Gemcitabine plus nab-paclitaxel until progression or given sequentially with 5-fluorouracile plus irinotecan (FOLFIRI.3) for first-line treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC): A randomized phase II study (PRODIGE 37-FIRGEMAX)

Author: Hortense Laharie-Mineur, Emilie Barbier, Anne Thirot Bidault, Côme Lepage, Romain Coriat, Eric Terrebonne, Marie-Claude Gouttebel, Jean-Baptiste Bachet, Yves Rinaldi, Patrick Texereau, Anne-Laure Pointet, David Malka, Faiza Khemissa, Alain Gratet, Julien Taieb, F. Ghiringhelli, Karine Bouhier-Leporrier, and Laurent Miglianico
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Chemotherapy, Pancreatic ductal adenocarcinoma, business.industry, medicine.medical_treatment, Phases of clinical research, Gemcitabine, First line treatment, Irinotecan, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, FOLFIRI, business, medicine.drug, Nab-paclitaxel
Abstract: 4107Background: Chemotherapy is effective in mPDAC but new approaches are still needed to improve patients (pts) survival and quality of life. We have previously published successful results of a s...
Published: 2018
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28. Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001–02)

Author: Gilles Breysacher, F. Masskouri, C. Choine, François Morvan, Pascal Hammel, Jean-François Seitz, P. Amoyal, J. Cretin, G. Gatineau-Sailliant, Christophe Locher, Thomas Aparicio, G. Bordes, O. Boulat, David Tougeron, I. Cumin, O. Berthelet, Anne Thirot Bidault, M. Pauwels, X. Moncoucy, Faiza Khemissa, F. Petit-Laurent, X. Adhoute, P. Prost, J.P. Lagasse, Jean-Louis Legoux, J. Ezenfis, N. Le Provost, Pierre Michel, A. Gueye, P. Pouderoux, G. Le Pessec, Julien Taieb, B. Landi, H. Fattouh, A. Azzedine, Mohamed Ramdani, Matthieu Schnee, Laurent Bedenne, Jean-Louis Jouve, C. Rebischung, J. Thaury, Ph. Rougier, C. Lobry, F. Guiliani, Jean-Baptiste Bachet, F. Ricard, L. Stefani, R. Mackiewicz, Dominique Genet, E. Cuillerier, C. Bineau, A.M. Queuniet, P. Couzigou, Jean-Marc Phelip, Eveline Boucher, B. Garcia, D. Cleau, M. Schneider, Iradj Sobhani, M. Mozer, Roger Faroux, Mohamed Gasmi, J. Charneau, Côme Lepage, Thierry Lecomte, Céline Lepère, D. Auby, Eric Terrebonne, R. Benoit, Emmanuel Mitry, D. Gargot, J. Martin, M. Baconnier, V. Derias, Achim Weber, Nadia Bouarioua, L. Chone, Catherine Lombard-Bohas, Patrick Texereau, B. Denis, May Mabro, Emilie Maillard, Sandrine Lavau-Denes, F. Di Fiore, C. Girault, J. Provençal, O. Bouche, F. Bonnetain, A. Gagnaire, Service de Gastro-entérologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Fédération Francophone de la Cancérologie Digestive, FFCD, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier de Blois (CHB), Hôpital Nord [CHU - APHM], Centre Hospitalier de Meaux, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de hépato-gastro-entérologie - cancérologie digestive [CH de Perpignan], Centre Hospitalier Saint Jean de Perpignan, Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Métropole Savoie [Chambéry], Hôpital pasteur [Colmar], Centre Hospitalier Régional d'Orléans (CHRO), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'oncologie médicale [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Duchenne, CH Boulogne sur Mer, Clinique Bonnefon, Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Henri Duffaut (Avignon), Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Paris], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP]
Subjects: Oncology, Male, medicine.medical_specialty, Leucovorin, colorectal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma, Irinotecan, chemotherapy, Gastroenterology, elderly, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, Progression-free survival, geriatric oncology, Aged, Proportional Hazards Models, Aged, 80 and over, business.industry, Hazard ratio, Hematology, Chemotherapy regimen, 3. Good health, Treatment Outcome, Fluorouracil, 030220 oncology & carcinogenesis, Multivariate Analysis, FOLFIRI, 030211 gastroenterology & hepatology, Camptothecin, Female, business, Colorectal Neoplasms, medicine.drug
Abstract: International audience; BACKGROUND:Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients.PATIENTS AND METHODS:Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR).RESULTS:From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%).CONCLUSION:In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2.CLINICALTRIALSGOV:NCT00303771.
Published: 2016
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29. High-Dose FOLFIRI plus Bevacizumab in the Treatment of Metastatic Colorectal Cancer Patients with Two Different UGT1A1 Genotypes: FFCD 0504 Study

Author: Laetitia Dahan, Marie-Anne Loriot, Pierre Michel, Pierre Luc Etienne, Faiza Khemissa, Gilles Breysacher, Sylvain Manfredi, Emilie Maillard, Karine Le Malicot, Jean Pierre Lafargue, Thierry Lecomte, Emmanuel Mitry, Jean Louis Legoux, Philippe Rougier, Cedric Lecaille, Olivier Bouché, Laurent Bedenne, and Thomas Aparicio
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Bevacizumab, Adolescent, Genotype, Colorectal cancer, Population, Leucovorin, Phases of clinical research, Gastroenterology, Disease-Free Survival, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Glucuronosyltransferase, Neoplasm Metastasis, education, Aged, education.field_of_study, Polymorphism, Genetic, business.industry, Middle Aged, medicine.disease, Interim analysis, Irinotecan, Oncology, Fluorouracil, FOLFIRI, Camptothecin, Female, business, Colorectal Neoplasms, medicine.drug
Abstract: High-dose FOLFIRI has an acceptable safety profile and promising efficacy. UDP-glucuronosyltransferase: (UGT1A1) polymorphism may be predictive of toxicity and efficacy of irinotecan. This phase II study aimed to evaluate the combination of high-dose FOLFIRI plus bevacizumab in patients with previously untreated metastatic colorectal cancer (MCRC) based on their UGT1A1 genotype. Patients with the UGT1A1 *1/*1 (group 1) or *1/*28 (group 2) genotype received bevacizumab plus high-dose FOLFIRI every 2 weeks. Using the Bryant and Day design with objective response rate and toxicity as the primary endpoints, 54 patients in each group were required with a planned interim analysis after inclusion of 17 patients per group. We planned to stop the trial at the interim analysis if ≤7 patients exhibited an objective response (OR) and/or ≥3 patients exhibited severe toxicity. At the interim analysis, ORs were higher than the number expected: 52.9% (group 1) and 58.8% (group 2). More than three toxic events occurred in both groups and, according to the interim analysis rule, the trial was closed due to unacceptable toxicity. Recruitment was stopped when 86 patients were included and an analysis on overall population was done for overall survival (OS) and progression-free survival (PFS). The median PFS was 10.7 months (group 1) and 10.4 months (group 2). The median OS was 25.5 months (group 1) and 23.9 months (group 2). This trial does not support the use of the intensive treatment with HD-FOLFIRI plus bevacizumab combination for MCRC in patients with the UGTA1*1/UGT1A1*1 or UGT1A1*1/UGT1A1*28 genotype. Mol Cancer Ther; 14(12); 2782–8. ©2015 AACR.
Published: 2015

30. Hepatitis E in decompensated alcoholic cirrhosis

Author: Emma Clair, Arnaud Pauwels, Anne-Marie Roque-Afonso, Hélène Agostini, Christophe Renou, Gilles Macaigne, Thierry Paupard, Bruno Lesgourgues, Agnes Pelaquier, Faiza Khemissa, Jean Henrion, and Yann Le Bricquir
Subjects: Liver Cirrhosis, medicine.medical_specialty, Alcoholic liver disease, Hepatology, Hepatitis, Alcoholic, business.industry, Hepatitis E, medicine.disease, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Liver Cirrhosis, Alcoholic, 030220 oncology & carcinogenesis, Internal medicine, medicine, Humans, 030211 gastroenterology & hepatology, business
Published: 2016
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31. Multicenter randomized phase II trial (BEVATOMOX) assessing the raltitrexed, oxaliplatin and bevacizumab combination versus FOLFOX6 bevacizumab as 2nd line treatment in metastatic colorectal cancer (mCRC)

Author: Fabienne Portales, Mohamed Ramdani, Eric Assenat, M. Ychou, Hélène Senellart, L. Mineur, S. Thezenas, Faiza Khemissa, S. Ellis, S. Jacquot, Thibault Mazard, and Emmanuelle Samalin
Subjects: Oncology, medicine.medical_specialty, Bevacizumab, business.industry, Colorectal cancer, Hematology, medicine.disease, Oxaliplatin, Internal medicine, medicine, Line (text file), business, Raltitrexed, medicine.drug
Published: 2017
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32. PRODIGE 51 - GASTFOX: Phase III randomised trial evaluating FOLFOX with or without DOCETAXEL (TFOX) as 1st line chemotherapy for locally advanced or metastatic oesophago-gastric adenocarcinoma

Author: Sylvain Manfredi, Emmanuelle Samalin, Pascal Artru, A. Zaanan, Faiza Khemissa, Y. Molin, François Ghiringhelli, Ph. Rougier, Julien Taieb, C. Louvet, Carole Monterymard, Olivier Romano, P. Bernard, Nabil Baba-Hamed, Samy Louafi, Benoist Chibaudel, Thomas Aparicio, David Tougeron, Pierre Michel, and O. Bouche
Subjects: Oncology, medicine.medical_specialty, Chemotherapy, business.industry, medicine.medical_treatment, Locally advanced, Hematology, 03 medical and health sciences, Gastric adenocarcinoma, 0302 clinical medicine, Docetaxel, FOLFOX, Internal medicine, Medicine, 030212 general & internal medicine, Line (text file), business, 030217 neurology & neurosurgery, medicine.drug
Published: 2017
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33. Impact of genetic polymorphisms of VEGF pathway on the response to bevacizumab in metastatic colorectal cancer (mCRC): Ancillary study of PRODIGE 9 trial

Author: Eric Francois, Karine Le Malicot, Laetitia Dahan, Julien Taieb, Jean-Baptiste Bachet, L. Cany, Roger Faroux, François Ghiringhelli, Valérie Boige, Olivier Bouché, Aurélie Fabre, Jean Francois Seitz, Jaafar Bennouna, Thomas Aparicio, Claire Mulot, Sylviane Olschwang, Faiza Khemissa, Camille Sibertin-Blanc, Stephane Jacquot, and Dominique Genet
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Bevacizumab, business.industry, Colorectal cancer, Ancillary Study, Single-nucleotide polymorphism, medicine.disease, digestive system diseases, Predictive factor, Vegf pathway, Internal medicine, Medicine, business, medicine.drug
Abstract: 3534Background: Bevacizumab (Bev) is widely used in mCRC but there is no validated predictive factor. Several studies have reported the impact of SNPs in the Vascular Endothelial Growth Factor-A (V...
Published: 2016
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34. Final results of PRODIGE 9, a randomized phase III comparing no treatment to bevacizumab maintenance during chemotherapy-free intervals in metastatic colorectal cancer

Author: Jean-Marc Phelip, Karine Le Malicot, Etienne Suc, François Ghiringhelli, Patrick Texereau, Eric Francois, Julien Taieb, Olivier Bouché, Françoise Desseigne, Faiza Khemissa, Valérie Boige, Jaafar Bennouna, Christian Borel, Jean-François Seitz, Dominique Genet, Jean-Louis Jouve, Stephane Jacquot, Thomas Aparicio, and Roger Faroux
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Chemotherapy, Bevacizumab, Colorectal cancer, business.industry, medicine.medical_treatment, medicine.disease, digestive system diseases, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, 030211 gastroenterology & hepatology, business, medicine.drug
Abstract: 3531Background: Conflicting results are reported for maintenance treatment with bevacizumab (bev) during chemotherapy free intervals (CFI) in metastatic colorectal cancer (mCRC). Methods: The objec...
Published: 2016
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35. FOLFIRINOX combined to targeted therapy according RAS status for colorectal cancer patients with liver metastases initially non-resectable: A phase II randomized Study—Prodige 14 – ACCORD 21 (METHEP-2), a unicancer GI trial

Author: Faiza Khemissa, Michel Rivoire, Eric Francois, Thomas Aparicio, Franck Audemar, Driffa Moussata, Philippe Houyau, Simon Thezenas, Marie-Pierre Galais, René Adam, Yves Becouarn, François Ghiringhelli, Eric Assenat, Rosine Guimbaud, Laurent Mineur, Olivier Bouché, Trevor Stanbury, Marc Ychou, and Anne Mercier-Blas
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Colorectal cancer, FOLFIRINOX, business.industry, medicine.medical_treatment, Induction chemotherapy, medicine.disease, Targeted therapy, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, 030220 oncology & carcinogenesis, Internal medicine, medicine, 030211 gastroenterology & hepatology, business
Abstract: 3512Background: Liver metastases (LM) from colorectal cancer (CRC) are initially resectable in only 10-15% of patients (pts). The conversion to resectability following induction chemotherapy is an ...
Published: 2016
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36. Comparative Efficacy and Long-Term Oncological Safety of Extended Right Hemicolectomy Versus Left Colectomy for Splenic Flexure Adenocarcinoma: A Systematic Review and Meta-Analysis

Author: Chaouch, Mohamed Ali, Krimi, Bassem, Gouader, Amine, Bhiri, Hanen, Barel, Elise, and Akouz, Faiza Khemissa
Abstract: Background Splenic flexure adenocarcinoma poses unique challenges in surgical management due to its location and lymphatic drainage. This study compared the efficacy and oncological safety of extended right hemicolectomy (ERC) and left colectomy (LC) for treating this condition.Methods This study followed the PRISMA and AMSTAR 2 guidelines. Key outcomes included postoperative mortality, morbidity, severe complications, operative results, pathological findings (R0 resection, lymph nodes), and oncological results (overall survival and disease-free survival at 3 and 5 years).Results Twelve non-randomised studies were included involving 1710 patients (713 ERC group, 997 LC group). The analysis showed that ERC was associated with more lymph nodes and a lower conversion rate. However, there were no significant differences between ERC and LC in terms of mortality, morbidity, severe complications, anastomotic leak, wound infection, ileus, reoperation, R0 resection, hospital stay, and overall and disease-free survival rates.Conclusions ERC and LC are comparable in terms of postoperative and long-term oncological outcomes for splenic flexure adenocarcinoma, with ERC potentially producing a higher lymph node harvest rate and a lower conversion rate. ERC could be suggested for a better stage of the disease and when the surgical team considers the laparoscopic approach.
Published: 2024
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37. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer

Author: Thierry, Conroy, Françoise, Desseigne, Marc, Ychou, Olivier, Bouché, Rosine, Guimbaud, Yves, Bécouarn, Antoine, Adenis, Jean-Luc, Raoul, Sophie, Gourgou-Bourgade, Christelle, de la Fouchardière, Jaafar, Bennouna, Jean-Baptiste, Bachet, Faiza, Khemissa-Akouz, Denis, Péré-Vergé, Catherine, Delbaldo, Eric, Assenat, Bruno, Chauffert, Pierre, Michel, Christine, Montoto-Grillot, Michel, Ducreux, C, Platini, Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), and Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, Antimetabolites, Antineoplastic, Organoplatinum Compounds, FOLFIRINOX, Leucovorin, Adenocarcinoma, Irinotecan, Gastroenterology, Deoxycytidine, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Neoplasm Metastasis, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Aged, Proportional Hazards Models, 0303 health sciences, Performance status, business.industry, Hazard ratio, General Medicine, Middle Aged, medicine.disease, Survival Analysis, Gemcitabine, 3. Good health, Oxaliplatin, Surgery, Pancreatic Neoplasms, 030220 oncology & carcinogenesis, Quality of Life, Camptothecin, Female, Folfirinox Regimen, Fluorouracil, business, Febrile neutropenia, medicine.drug, Follow-Up Studies
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
Published: 2011

38. PRODIGE 20: Bevacizumab + chemotherapy (BEV-CT) versus chemotherapy alone (CT) in elderly patients (pts) with untreated metastatic colorectal cancer (mCRC)—A randomized phase II trial

Author: Farid El Hajbi, Faiza Khemissa, Sylvie Kirscher, Christophe Locher, Dominique Genet, Julien Taieb, Thomas Aparicio, Yves Rinaldi, Pierre-Luc Etienne, Thierry Lecomte, Roger Faroux, Olivier Bouché, Laurent Bedenne, Alice Oden-Gangloff, Elena Paillaud, M. Baconnier, Emilie Maillard, Sandrine Lavau-Denes, Eric Francois, and Frederic Retornaz
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Chemotherapy, Bevacizumab, Colorectal cancer, business.industry, medicine.medical_treatment, medicine.disease, digestive system diseases, Capecitabine, Internal medicine, medicine, business, medicine.drug
Abstract: 3541 Background: AVEX study has demonstrated increased progression-free survival (PFS) with capecitabine + bevacizumab compared to capecitabine alone in pts aged over 70 with mCRC. The treatment wi...
Published: 2015
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39. 4523 Usefulness of associating a lower video push enteroscopy with an upper tract enteroscopy in unexplained gastrointestinal bleeding

Author: Paul Bauret, Faiza Khemissa, and Dominique Larrey
Subjects: Enteroscopy, medicine.medical_specialty, Gastrointestinal bleeding, medicine.diagnostic_test, Endoscope, business.industry, Gastroenterology, Ileum, medicine.disease, Surgery, Lesion, medicine.anatomical_structure, Iron-deficiency anemia, medicine, Push enteroscopy, Fluoroscopy, Radiology, Nuclear Medicine and imaging, medicine.symptom, business
Abstract: In patients with unexplained gastrointestinal bleeding upper push enteroscopy shows no lesion in 25-62 % of cases (1). These results may be due to an incomplete examination of the digestive tract (ileum and large bowel). Aim of the study: To assess the benefit of the lower tract enteroscopy in unexplained gastrointestinal bleeding. Patients and methods: Between October 1994 and December 1998 every patient with no lesion found after upper video push enteroscopy (Olympus SIF 100) or suspected of presenting numerous intestinal lesions had systematiccaly a lower tract, retrograde, push enteroscopy performed with a colonic overtube during the same anaesthesia on a fluoroscopy table. Results: Among 102 prospectively studied patients, 97 had a retrograde ileoscopy. 1) Double way push enteroscopy showed a potential bleeding lesion in 39 (40 %) patients (55 % of patients with macroscopic digestive bleeding and 26 % of patients with chronic iron deficiency anemia); 51 % of these lesions were within reach of a standard endoscope. 2) The lower tract enteroscopy showed a lesion in 12 (12 %) patients; 2/3 of these lesions were accessible to a standard colonoscope. 3) An ileal lesion was found in 4 (4 %) patients (30 cm above the ileocaecal valve in 3 patients, 130 cm above the valve in 1 patient). Conclusion: No associating a lower enteroscopy with an upper video push enteroscopy leads to miss 31 % of the diagnosticable lesions in 12 % of patients with unexplained gastrointestinal bleeding; only 4 % of patients have lesions located in the distal ileum. (1) Wayne JD. Gastrointest Endosc 1997; 46: 247.
Published: 2000
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40. Bevacizumab Maintenance Versus No Maintenance During Chemotherapy-Free Intervals in Metastatic Colorectal Cancer: A Randomized Phase III Trial (PRODIGE 9).

Author: Aparicio T, Ghiringhelli F, Boige V, Le Malicot K, Taieb J, Bouché O, Phelip JM, François E, Borel C, Faroux R, Dahan L, Jacquot S, Genet D, Khemissa F, Suc E, Desseigne F, Texereau P, Lepage C, and Bennouna J
Subjects: Aged, Colorectal Neoplasms mortality, Colorectal Neoplasms pathology, Disease-Free Survival, Female, Humans, Induction Chemotherapy, Male, Middle Aged, Neoplasm Metastasis, Time Factors, Antineoplastic Agents, Immunological therapeutic use, Bevacizumab therapeutic use, Colorectal Neoplasms drug therapy
Abstract: Purpose Conflicting results are reported for maintenance treatment with bevacizumab during chemotherapy-free intervals (CFI) in metastatic colorectal cancer after induction chemotherapy. Patients and Methods In this open-label, phase III, randomized controlled trial, we compared the tumor control duration (TCD) observed with bevacizumab maintenance and with no treatment (observation) during CFI subsequent to induction chemotherapy with 12 cycles of fluorouracil, leucovorin, and irinotecan plus bevacizumab. After disease progression, the induction regimen was repeated for eight cycles, followed by a new CFI. Results From March 2010 to July 2013, 491 patients were randomly assigned. Disease progression or death occurred during induction chemotherapy in 85 patients (17%); 261 patients (53%) had at least one reinduction, 107 (22%) had two reinductions, and 56 (11%) had three or more reinductions. The median TCD was 15 months in both groups; the median progression-free survival (PFS) from randomization was 9.2 and 8.9 months in the maintenance group and observation groups, respectively. The TCD observed in both groups was higher compared with the TCD hypotheses of the trial. The median overall survival (OS) was 21.7 and 22.0 months in the maintenance and observation groups, respectively. In the per-protocol population, defined as patients with at least one reinduction after the first progression, the median duration of the first CFI was 4.3 months in both arms; the median TCD was 17.8 and 23.3 months ( P = .339), the median PFS was 9.9 and 9.5 months, and the median OS was 27.6 and 28.5 months in the maintenance and observation groups, respectively. Multivariable analysis revealed that female gender, WHO performance status ≥ 2, and unresected primary tumors were associated with a shorter TCD. Conclusion Bevacizumab maintenance monotherapy did not improve TCD, CFI duration, PFS, or OS.
Published: 2018
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