المؤلفون: Motzer, Robert, Alekseev, Boris, Rha, Sun-Young, Porta, Camillo, Eto, Masatoshi, Powles, Thomas, Grünwald, Viktor, Hutson, Thomas E, Kopyltsov, Evgeny, Méndez-Vidal, María J, Kozlov, Vadim, Alyasova, Anna, Hong, Sung-Hoo, Kapoor, Anil, Alonso Gordoa, Teresa, Merchan, Jaime R, Winquist, Eric, Maroto, Pablo, Goh, Jeffrey C, Kim, Miso, Gurney, Howard, Patel, Vijay, Peer, Avivit, Procopio, Giuseppe, Takagi, Toshio, Melichar, Bohuslav, Rolland, Frederic, De Giorgi, Ugo, Wong, Shirley, Bedke, Jens, Schmidinger, Manuela, Dutcus, Corina E, Smith, Alan D, Dutta, Lea, Mody, Kalgi, Perini, Rodolfo F, Xing, Dongyuan, Choueiri, Toni K, CLEAR Trial Investigators

المساهمون: Gennigens, Christine

المصدر: New England Journal of Medicine, 384 (14), 1289 - 1300 (2021-04-08)

مصطلحات موضوعية: Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Phenylurea Compounds, Programmed Cell Death 1 Receptor, Protein Kinase Inhibitors, Quinolines, Everolimus, pembrolizumab, lenvatinib, Sunitinib, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized/administration & dosage, Antibodies, Monoclonal, Humanized/adverse effects, Antineoplastic Agents/adverse effects, Antineoplastic Agents/therapeutic use, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Carcinoma, Renal Cell/drug therapy, Carcinoma, Renal Cell/mortality, Everolimus/administration & dosage, Everolimus/adverse effects, Female, Humans, Kidney Neoplasms/drug therapy, Kidney Neoplasms/mortality, Male, Middle Aged, Phenylurea Compounds/administration & dosage, Phenylurea Compounds/adverse effects, Programmed Cell Death 1 Receptor/antagonists & inhibitors, Progression-Free Survival, Protein Kinase Inhibitors/therapeutic use, Quinolines/administration & dosage, Quinolines/adverse effects, Sunitinib/adverse effects, Sunitinib/therapeutic use, Survival Analysis, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Renal Cell, Kidney Neoplasms, Medicine (all), General Medicine, Human health sciences, Oncology, Sciences de la santé humaine, Oncologie

الوصف: [en] BACKGROUND: Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib is unclear.METHODS: In this phase 3 trial, we randomly assigned (in a 1:1:1 ratio) patients with advanced renal cell carcinoma and no previous systemic therapy to receive lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously once every 3 weeks), lenvatinib (18 mg orally once daily) plus everolimus (5 mg orally once daily), or sunitinib (50 mg orally once daily, alternating 4 weeks receiving treatment and 2 weeks without treatment). The primary end point was progression-free survival, as assessed by an independent review committee in accordance with Response Evaluation Criteria in Solid Tumors, version 1.1. Overall survival and safety were also evaluated.RESULTS: A total of 1069 patients were randomly assigned to receive lenvatinib plus pembrolizumab (355 patients), lenvatinib plus everolimus (357), or sunitinib (357). Progression-free survival was longer with lenvatinib plus pembrolizumab than with sunitinib (median, 23.9 vs. 9.2 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.32 to 0.49; P<0.001) and was longer with lenvatinib plus everolimus than with sunitinib (median, 14.7 vs. 9.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.80; P<0.001). Overall survival was longer with lenvatinib plus pembrolizumab than with sunitinib (hazard ratio for death, 0.66; 95% CI, 0.49 to 0.88; P = 0.005) but was not longer with lenvatinib plus everolimus than with sunitinib (hazard ratio, 1.15; 95% CI, 0.88 to 1.50; P = 0.30). Grade 3 or higher adverse events emerged or worsened during treatment in 82.4% of the patients who received lenvatinib plus pembrolizumab, 83.1% of those who received lenvatinib plus everolimus, and 71.8% of those who received sunitinib. Grade 3 or higher adverse events occurring in at least 10% of the patients in any group included hypertension, diarrhea, and elevated lipase levels.CONCLUSIONS: Lenvatinib plus pembrolizumab was associated with significantly longer progression-free survival and overall survival than sunitinib. (Funded by Eisai and Merck Sharp and Dohme; CLEAR ClinicalTrials.gov number, NCT02811861.).

العلاقة: http://www.nejm.org/doi/pdf/10.1056/NEJMoa2035716Test; urn:issn:0028-4793; urn:issn:1533-4406

الوصول الحر: https://orbi.uliege.be/handle/2268/300816Test

المؤلفون: Valérie Vilgrain, Helena Pereira, Eric Assenat, Boris Guiu, Alina Diana Ilonca, Georges-Philippe Pageaux, Annie Sibert, Mohamed Bouattour, Rachida Lebtahi, Wassim Allaham, Hélène Barraud, Valérie Laurent, Elodie Mathias, Jean-Pierre Bronowicki, Jean-Pierre Tasu, Rémy Perdrisot, Christine Silvain, René Gerolami, Olivier Mundler, Jean-Francois Seitz, Vincent Vidal, Christophe Aubé, Frédéric Oberti, Olivier Couturier, Isabelle Brenot-Rossi, Jean-Luc Raoul, Anthony Sarran, Charlotte Costentin, Emmanuel Itti, Alain Luciani, René Adam, Maïté Lewin, Didier Samuel, Maxime Ronot, Aurelia Dinut, Laurent Castera, Gilles Chatellier, Elisabeth Delhom - Christol, Alina D Ilonca, Julie Lonjon, Mohamed Abdel-Rehim, Arnaud Dieudonné, Christophe Bazin, Carine Chagneau-Derrode, Patrick Borentain, Antoine Bouvier, Laurent Vervueren, Julia Chalaye, Hicham Kobeiter, Julien Edeline, Etienne Garin, Yan Rolland, Isabelle Archambeaud, Thomas Eugene, Eric Frampas, Christophe Cassinotto, Martine Guyot, Jean-Baptiste Hiriart, Bruno Lapuyade, Julien Vergniol, Philippe Bachellier, Julien Detour, Bernard Duclos, Michel Greget, Francois Habersetzer, Alessio Imperiale, Philippe Merle, Agnès Rode, Julie Morvan, Eric Nguyen-Khac, Thierry Yzet, Guillaume Baudin, Patrick Chevallier, Abakar Mahamat, Thierry Piche, Micheline Razzouk, Patrick Hillon, Romaric Loffroy, Michel Toubeau, Julie Vincent, Gabriele Barabino, Nadia Bouarioua, Muriel Cuilleron, Marie Ecochard, Nathalie Prevot-Bitot, Vincent Leroy, Julie Roux, Christian Sengel, Valérie Bourcier, Nathalie Ganne-Carrie, Olivier Seror, Sylvie Costo, Thông Dao, Jean-Pierre Pelage, Jérôme Dumortier, Francesco Giammarile, Pierre-Jean Valette, Nadia Ghazzar, Olivier Pellerin, Julien Taieb, Pierre Weinmann, Alexandra Heurgue-Berlot, Claude Marcus, Daniele Sommacale, Maria-Angéla Castilla-Lièvre, Sophie Maitre, Lysiane Marthey

المساهمون: Hôpital Beaujon, Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Eloi, Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)

المصدر: Lancet Oncology
Lancet Oncology, Elsevier, 2017, 18 (12), pp.1624-1636. ⟨10.1016/S1470-2045(17)30683-6⟩

مصطلحات موضوعية: Male, medicine.medical_treatment, Brachytherapy, Administration, Oral, Kaplan-Meier Estimate, Liver transplantation, Gastroenterology, 0302 clinical medicine, Yttrium Radioisotopes, MESH: Carcinoma, Hepatocellular/drug therapy, education.field_of_study, Liver Neoplasms, Radiotherapy Dosage, MESH: Carcinoma, Hepatocellular/radiotherapy, Middle Aged, Sorafenib, Microspheres, MESH: Niacinamide/analogs & derivatives, 3. Good health, MESH: Liver Neoplasms/drug therapy, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Female, 030211 gastroenterology & hepatology, MESH: Phenylurea Compounds/administration & dosage, Liver cancer, medicine.drug, Adult, Niacinamide, medicine.medical_specialty, Carcinoma, Hepatocellular, Population, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, Drug Administration Schedule, 03 medical and health sciences, Internal medicine, medicine, Carcinoma, Humans, Neoplasm Invasiveness, education, Aged, Neoplasm Staging, Dose-Response Relationship, Drug, Performance status, business.industry, Phenylurea Compounds, medicine.disease, Survival Analysis, Surgery, MESH: Yttrium Radioisotopes/therapeutic use, Liver function, business, Follow-Up Studies

الوصف: Summary Background Sorafenib is the recommended treatment for patients with advanced hepatocellular carcinoma. We aimed to compare the efficacy and safety of sorafenib to that of selective internal radiotherapy (SIRT) with yttrium-90 ( 90 Y) resin microspheres in patients with hepatocellular carcinoma. Methods SARAH was a multicentre, open-label, randomised, controlled, investigator-initiated, phase 3 trial done at 25 centres specialising in liver diseases in France. Patients were eligible if they were aged at least 18 years with a life expectancy greater than 3 months, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, Child-Pugh liver function class A or B score of 7 or lower, and locally advanced hepatocellular carcinoma (Barcelona Clinic Liver Cancer [BCLC] stage C), or new hepatocellular carcinoma not eligible for surgical resection, liver transplantation, or thermal ablation after a previously cured hepatocellular carcinoma (cured by surgery or thermoablative therapy), or hepatocellular carcinoma with two unsuccessful rounds of transarterial chemoembolisation. Patients were randomly assigned (1:1) by a permutated block method with block sizes two and four to receive continuous oral sorafenib (400 mg twice daily) or SIRT with 90 Y-loaded resin microspheres 2–5 weeks after randomisation. Patients were stratified according to randomising centre, ECOG performance status, previous transarterial chemoembolisation, and presence of macroscopic vascular invasion. The primary endpoint was overall survival. Analyses were done on the intention-to-treat population; safety was assessed in all patients who received at least one dose of sorafenib or underwent at least one of the SIRT work-up exams. This study has been completed and the final results are reported here. The trial is registered with ClinicalTrials.gov, number NCT01482442. Findings Between Dec 5, 2011, and March 12, 2015, 467 patients were randomly assigned; after eight patients withdrew consent, 237 were assigned to SIRT and 222 to sorafenib. In the SIRT group, 53 (22%) of 237 patients did not receive SIRT; 26 (49%) of these 53 patients were treated with sorafenib. Median follow-up was 27·9 months (IQR 21·9–33·6) in the SIRT group and 28·1 months (20·0–35·3) in the sorafenib group. Median overall survival was 8·0 months (95% CI 6·7–9·9) in the SIRT group versus 9·9 months (8·7–11·4) in the sorafenib group (hazard ratio 1·15 [95% CI 0·94–1·41] for SIRT vs sorafenib; p=0·18). In the safety population, at least one serious adverse event was reported in 174 (77%) of 226 patients in the SIRT group and in 176 (82%) of 216 in the sorafenib group. The most frequent grade 3 or worse treatment-related adverse events were fatigue (20 [9%] vs 41 [19%]), liver dysfunction (25 [11%] vs 27 [13%]), increased laboratory liver values (20 [9%] vs 16 [7%]), haematological abnormalities (23 [10%] vs 30 [14%]), diarrhoea (three [1%] vs 30 [14%]), abdominal pain (six [3%] vs 14 [6%]), increased creatinine (four [2%] vs 12 [6%]), and hand-foot skin reaction (one [ vs 12 [6%]). 19 deaths in the SIRT group and 12 in the sorafenib group were deemed to be treatment related. Interpretation In patients with locally advanced or intermediate-stage hepatocellular carcinoma after unsuccessful transarterial chemoembolisation, overall survival did not significantly differ between the two groups. Quality of life and tolerance might help when choosing between the two treatments. Funding Sirtex Medical Inc.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::37960b5209b2b33f51aee9e80e06e797Test
https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01727346Test

المؤلفون: Pierre Laurent-Puig, Sylvain Poujol, Françoise Desseigne, S. Thezenas, Thibault Mazard, Evelyne Crapez, Emmanuelle Samalin, E. Francois, Antoine Adenis, T. Conroy, J.F. Seitz, Julien Taieb, M.P. Galais, Jaafar Bennouna, F. Boissière, Marc Ychou, Eric Assenat, O. Bouche, Frédéric Bibeau

المساهمون: CRLCC Val d'Aurelle - Paul Lamarque, Hôpital universitaire Robert Debré [Reims], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, CIC - HEGP (CIC 1418), 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)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), 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), CRLC Val d'Aurelle-Paul Lamarque, 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), Université Lille Nord de France (COMUE)-UNICANCER, UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), 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), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, CRLCC Oscar Lambret, Institut de Cancérologie de l'Ouest, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)

المصدر: British Journal of Cancer
Breast Cancer Research and Treatment
Breast Cancer Research and Treatment, 2014, 110, pp.1148--54. ⟨10.1038/bjc.2013.813⟩
Breast Cancer Research and Treatment, Springer Verlag, 2014, 110, pp.1148--54. ⟨10.1038/bjc.2013.813⟩

مصطلحات موضوعية: Male, Cancer Research, Colorectal cancer, medicine.medical_treatment, Camptothecin/administration & dosage/analogs & derivatives, Gastroenterology, tyrosine kinase inhibitor, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, 80 and over, clinic, Aged, 80 and over, education.field_of_study, metastatic colorectal cancer, ras Proteins/*genetics, Mutation, Middle Aged, Sorafenib, 3. Good health, Oncology, Disease Progression, Female, Colorectal Neoplasms, medicine.drug, Adult, Niacinamide, medicine.medical_specialty, Niacinamide/administration & dosage/analogs & derivatives, Population, Colorectal Neoplasms/*drug therapy/genetics, [SDV.CAN]Life Sciences [q-bio]/Cancer, Neutropenia, Irinotecan, Disease-Free Survival, Proto-Oncogene Proteins p21(ras), Internal medicine, Proto-Oncogene Proteins, medicine, Humans, Antineoplastic Combined Chemotherapy Protocols/*therapeutic use, education, neoplasms, Aged, Chemotherapy, business.industry, Phenylurea Compounds, medicine.disease, digestive system diseases, Surgery, KRAS gene mutation, Regimen, Phenylurea Compounds/administration & dosage, Clinical Study, ras Proteins, Proto-Oncogene Proteins/*genetics, Camptothecin, business

الوصف: IMPACT: 5.922; International audience; BACKGROUND: This trial evaluated the feasibility and efficacy of combined sorafenib and irinotecan (NEXIRI) as second- or later-line treatment of patients with KRAS-mutated metastatic colorectal cancer (mCRC), who had progressed after irinotecan-based chemotherapy. METHODS: In Phase I, in a 3+3 dose escalation schedule, patients received irinotecan (125, 150 or 180 mg m(-2) every 2 weeks), in combination with 400 mg sorafenib b.d. The primary end point was the maximum-tolerated dose of irinotecan. In Phase II, the primary end point was disease control rate (DCR). Secondary end points were progression-free survival (PFS), overall survival (OS) and toxicity. RESULTS: Phase I included 10 patients (median age 63 (49-73)); no dose-limiting toxicity was seen. In Phase II, 54 patients (median age 60 (43-80) years) received irinotecan 180 mg m(-)(2) every 2 weeks with sorafenib 400 mg b.d. Nine patients (17%) remained on full-dose sorafenib. The DCR was 64.9% (95% CI, 51-77). Median PFS and OS were 3.7 (95% CI, 3.2-4.7) and 8.0 (95% CI, 4.8-9.7) months, respectively. Toxicities included Grade 3 diarrhoea (37%), neutropenia (18%), hand-foot syndrome (13%) and Grade 4 neutropenia (17%). CONCLUSION: The NEXIRI regimen showed promising activity as second- or later-line treatment in this heavily pretreated mCRC population (ClinicalTrials.gov NCT00989469).

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0de27d5b42bd45149c4970a8cb5a2512Test
http://europepmc.org/articles/PMC3950852Test

المؤلفون: Antoine Hollebecque, Sonia Extremera, Gilles Salles, Vicente Alfaro, Sandrine Aspeslagh, Mark N. Stein, Emmanuel Gyan, Salvador Fudio, Rastilav Bahleda, Arturo Soto-Matos, Jean-Charles Soria

المساهمون: Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical Oncology

المصدر: Anti-Cancer Drugs
Anti-Cancer Drugs, Lippincott, Williams & Wilkins, 2016, ⟨10.1097/CAD.0000000000000457⟩

مصطلحات موضوعية: 0301 basic medicine, Oncology, Male, Cancer Research, Lymphoma, Administration, Oral, Deoxycytidine, Gastroenterology, Depsipeptides/administration & dosage, 0302 clinical medicine, Depsipeptides, Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Medicine, Pharmacology (medical), Prospective Studies, Fatigue, Nausea, Antineoplastic Combined Chemotherapy Protocols/administration & dosage, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, Toxicity, Vomiting, young adult, Female, France, medicine.symptom, medicine.drug, Niacinamide, Sorafenib, Adult, medicine.medical_specialty, Patients, [SDV.CAN]Life Sciences [q-bio]/Cancer, Peptides, Cyclic, 03 medical and health sciences, Niacinamide/administration & dosage, Refractory, Internal medicine, Humans, Adverse effect, Deoxycytidine/administration & dosage, Aged, Lymphoma/drug therapy, Pharmacology, therapy, Dose-Response Relationship, Drug, business.industry, Phenylurea Compounds, toxicity, medicine.disease, Gemcitabine, Thrombocytopenia, Neoplasms/drug therapy, SORAFENIB, 030104 developmental biology, Phenylurea Compounds/administration & dosage, Erythema, business, aged, 80 and over

الوصف: International audience; This phase I trial evaluated the combination of the marine-derived cyclodepsipeptide plitidepsin (trade name Aplidin) with sorafenib or gemcitabine in advanced cancer and lymphoma patients. The study included two treatment arms: a sorafenib/plitidepsin (S/P) and a gemcitabine/plitidepsin (G/P) arm. In the S/P arm, patients were treated orally with sorafenib continuous dosing at two dose levels (DL1: 200 mg twice daily and DL2: 400 mg twice daily) combined with plitidepsin (1.8 mg/m, day 1, day 8, day 15, and, q4wk, intravenously). In the G/P arm, patients with solid tumors or lymphoma were treated at four different DLs with a combination of gemcitabine (DL1: 750 mg/m, DL2-DL4: 1000 mg/m) and plitidepsin (DL1-DL2: 1.8 mg/m; DL3: 2.4 mg/m; DL4: 3 mg/m). Both agents were administered intravenously on day 1, day 8, day 15, and, q4wk. Forty-four patients were evaluable for safety and toxicity. The safety of the combination of plitidepsin with sorafenib or gemcitabine was manageable. Most adverse events (AEs) were mild; no grade 4 treatment-related AEs were reported in any of the groups (except for one grade 4 thrombocytopenia in the gemcitabine arm). The most frequently reported study drug-related (or of unknown relationship) AEs were palmar-plantar erythrodysesthesia, erythema, nausea, vomiting, and fatigue in the S/P arm and nausea, fatigue, and vomiting in the G/P arm. In the S/P arm, one dose-limiting toxicity occurred in two out of six patients treated at the maximum dose tested (DL2): palmar-plantar erythrodysesthesia and grade 2 aspartate aminotransferase/alanine aminotransferase increase that resulted in omission of days 8 and 15 plitidepsin infusions. In the G/P arm, one dose-limiting toxicity occurred in two out of six patients at DL4: grade 2 alanine aminotransferase increase resulted in omission of days 8 and 15 plitidepsin infusions and grade 4 thrombocytopenia. The recommended dose for the combination of plitidepsin with sorafenib was not defined because of a sponsor decision (no expansion cohort to confirm) and for plitidepsin with gemcitabine, it was 2.4 mg/m plitidepsin with 1000 mg/m gemcitabine. In the S/P group, objective disease responses were not observed; however, disease stabilization (\textgreater/=3months) was observed in four patients. In the gemcitabine group, two lymphoma patients showed an objective response (partial response and complete response) and nine patients showed disease stabilization (\textgreater/=3months). Combining plitidepsin with gemcitabine and sorafenib is feasible for advanced cancer patients; some objective responses were observed in heavily pretreated lymphoma patients

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a23b85d24896c8e6b050b4cfb9ec050cTest
https://hal.archives-ouvertes.fr/hal-01791282Test

المؤلفون: Lieveke Ameye, Raphaël Maréchal, Amélie Deleporte, Irina Vierasu, Erwin Woff, Thomas Guiot, Camilo Garcia, Alain Hendlisz, Thierry Delaunoit, Gauthier Demolin, Namur Gauthier, Renaud Lhommel, Patrick Flamen, Marc Van den Eynde, Stéphane Holbrechts

المساهمون: UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Service de médecine nucléaire, UCL - (SLuc) Unité d'oncologie médicale, UCL - (SLuc) Centre du cancer

المصدر: European Journal of Nuclear Medicine and Molecular Imaging
European Journal of Nuclear Medicine and Molecular Imaging, Vol. 43, p. 1792-1801 (2016)
European journal of nuclear medicine and molecular imaging, 43 (10

مصطلحات موضوعية: Oncology, Male, Colorectal cancer, medicine.medical_treatment, Phenylurea Compounds -- administration & dosage, 030218 nuclear medicine & medical imaging, Targeted therapy, Tumoral heterogeneity, 0302 clinical medicine, Positron Emission Tomography Computed Tomography, Antineoplastic Combined Chemotherapy Protocols, Radiopharmaceuticals -- pharmacokinetics, Molecular Targeted Therapy, Fluorodeoxyglucose F18 -- pharmacokinetics, Imagerie médicale, radiologie, tomographie, Metastatic colorectal cancer, Colorectal Neoplasms -- diagnostic imaging -- drug therapy -- secondary, General Medicine, Middle Aged, Sorafenib, Treatment Outcome, Drug Monitoring -- methods, Radiology Nuclear Medicine and imaging, 030220 oncology & carcinogenesis, Fdg pet ct, Female, Original Article, Niacinamide -- administration & dosage -- analogs & derivatives, medicine.symptom, Drug Monitoring, Colorectal Neoplasms, medicine.drug, Adult, Niacinamide, medicine.medical_specialty, Sensitivity and Specificity, Capecitabine, Lesion, FDG PET-CT, 03 medical and health sciences, Fluorodeoxyglucose F18, Internal medicine, medicine, Volume reduction, Humans, Molecular Targeted Therapy -- methods, Radiology, Nuclear Medicine and imaging, Aged, business.industry, Phenylurea Compounds, Reproducibility of Results, Positron Emission Tomography Computed Tomography -- methods, medicine.disease, Capecitabine -- administration & dosage, Discontinuation, Antineoplastic Combined Chemotherapy Protocols -- administration & dosage, Radiopharmaceuticals, business, Early metabolic response assessment

الوصف: Introduction: The introduction of targeted drugs has had a significant impact on the approach to assessing tumour response. These drugs often induce a rapid cytostatic effect associated with a less pronounced and slower tumoural volume reduction, thereby impairing the correlation between the absence of tumour shrinkage and the patient’s unlikelihood of benefit. The aim of the study was to assess the predictive value of early metabolic response (mR) evaluation after one cycle, and its interlesional heterogeneity to a later metabolic and morphological response assessment performed after three cycles in metastatic colorectal cancer (mCRC) patients treated with combined sorafenib and capecitabine. Methods: This substudy was performed within the framework of a wider prospective multicenter study on the predictive value of early FDG PET-CT response assessment (SoMore study). A lesion-based response analysis was performed, including all measurable lesions identified on the baseline PET. On a per-patient basis, a descriptive 4-class response categorization was applied based upon the presence and proportion of non-responding lesions. For dichotomic response comparison, all patients with at least one resistant lesion were classified as non-responding. Results: On baseline FDG PET-CT, 124 measurable “target” lesions were identified in 38 patients. Early mR assessments showed 18 patients (47 %) without treatment resistant lesions and 12 patients (32 %) with interlesional response heterogeneity. The NPV and PPV of early mR were 85 % (35/41) and 84 % (70/83), respectively, on a per-lesion basis and 95 % (19/20) and 72 % (13/18), respectively, on a dichotomized per-patient basis. Conclusions: Early mR assessment performed after one cycle of sorafenib-capecitabine in mCRC is highly predictive of non-response at a standard response assessment time. The high NPV (95 %) of early mR could be useful as the basis for early treatment discontinuation or adaptation to spare patients from exposure to non-effective drugs.
SCOPUS: ar.j
info:eu-repo/semantics/published

وصف الملف: 1 full-text file(s): application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3e0aa1f3a5363635b991f75146123099Test
https://pubmed.ncbi.nlm.nih.gov/27072811Test

المؤلفون: Thomas Hundsberger, Dietrich Py, N. Dunkel, A. Ben Aissa, Maria Vargas, Andreas F. Hottinger, Karl Lothard Schaller, Vittoria Espeli, Nicolas Mach, D. Squiban, Damien C. Weber, A Bodmer

المصدر: British Journal of Cancer, vol. 110, no. 11, pp. 2655-2661
British Journal of Cancer
British Journal of Cancer, Vol. 110, No 11 (2014) pp. 2655-2661

مصطلحات موضوعية: Oncology, Male, Cancer Research, medicine.medical_treatment, Pharmacology, urologic and male genital diseases, radiation therapy, tyrosine kinase inhibitor, Antineoplastic Combined Chemotherapy Protocols, heterocyclic compounds, ddc:616, Glioblastoma/mortality/therapy, Brain Neoplasms, Chemoradiotherapy, Middle Aged, Sorafenib, Brain Neoplasms/mortality/therapy, female genital diseases and pregnancy complications, Phase i study, Dacarbazine, Treatment Outcome, Female, Corrigendum, high-grade glioma, medicine.drug, Adult, Niacinamide, medicine.medical_specialty, Niacinamide/administration & dosage/analogs & derivatives, Maximum Tolerated Dose, ddc:616.0757, pharmacokinetic study, Disease-Free Survival, Glioma, Internal medicine, medicine, Temozolomide, Humans, neoplasms, Aged, business.industry, Phenylurea Compounds, medicine.disease, digestive system diseases, ddc:616.8, First line treatment, Radiation therapy, Phenylurea Compounds/administration & dosage, Clinical Study, Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics/therapeutic use/toxicity, Dacarbazine/administration & dosage/analogs & derivatives, business, Glioblastoma

الوصف: BACKGROUND: Sorafenib (Sb) is a multiple kinase inhibitor targeting both tumour cell proliferation and angiogenesis that may further act as a potent radiosensitizer by arresting cells in the most radiosensitive cell cycle phase. This phase I open-label, noncontrolled dose escalation study was performed to determine the safety and maximum tolerated dose (MTD) of Sb in combination with radiation therapy (RT) and temozolomide (TMZ) in 17 patients with newly diagnosed high-grade glioma. METHODS: Patients were treated with RT (60 Gy in 2 Gy fractions) combined with TMZ 75 mg m(-2) daily, and Sb administered at three dose levels (200 mg daily, 200 mg BID, and 400 mg BID) starting on day 8 of RT. Thirty days after the end of RT, patients received monthly TMZ (150-200 mg m(-2) D1-5/28) and Sb (400 mg BID). Pharmacokinetic (PK) analyses were performed on day 8 (TMZ) and on day 21 (TMZ&Sb) (Clinicaltrials ID: NCT00884416). RESULTS: The MTD of Sb was established at 200 mg BID. Dose-limiting toxicities included thrombocytopenia (two patients), diarrhoea (one patient) and hypercholesterolaemia (one patient). Sb administration did not affect the mean area under the curve(0-24) and mean Cmax of TMZ and its metabolite 5-amino-imidazole-4-carboxamide (AIC). Tmax of both TMZ and AIC was delayed from 0.75 (TMZ alone) to 1.5 h (combined TMZ/Sb). The median progression-free survival was 7.9 months (95% confidence interval (CI): 5.4-14.55), and the median overall survival was 17.8 months (95% CI: 14.7-25.6). CONCLUSIONS: Although Sb can be combined with RT and TMZ, significant side effects and moderate outcome results do not support further clinical development in malignant gliomas. The robust PK data of the TMZ/Sb combination could be useful in other cancer settings.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5769967950cf20f0072e4f151af7bd83Test
https://serval.unil.ch/resource/serval:BIB_A3EE92645B9C.P001/REF.pdfTest

المؤلفون: Céline Gongora

المساهمون: 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), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), 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)

المصدر: Molecular Cancer Therapeutics
Molecular Cancer Therapeutics, American Association for Cancer Research, 2014, 13, pp.764. ⟨10.1158/1535-7163.MCT-13-1026⟩

مصطلحات موضوعية: Sorafenib, Cancer Research, Abcg2, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pharmacology, urologic and male genital diseases, 03 medical and health sciences, 0302 clinical medicine, Colorectal Neoplasms/*drug therapy, medicine, Distribution (pharmacology), Animals, Humans, heterocyclic compounds, Neoplasm Proteins/*genetics, neoplasms, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, biology, Chemistry, Resistance response, ATP-Binding Cassette Transporters/*genetics, Camptothecin/*analogs & derivatives, Phenylurea Compounds/*administration & dosage, Blood proteins, female genital diseases and pregnancy complications, digestive system diseases, 3. Good health, Irinotecan, Niacinamide/*analogs & derivatives, Oncology, 030220 oncology & carcinogenesis, biology.protein, Steady state (chemistry), medicine.drug

الوصف: We are aware that sorafenib binds to plasma proteins. At steady state, when sorafenib is orally administered at 800 mg/d, accumulation ratios are 5.7 to 6.4, indicating that it has a good distribution range. Of note, 90% of sorafenib is bound to the plasma proteins ([1][1]), but the large

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a5f54a702471cb25ea39806909e64549Test
https://hal.umontpellier.fr/hal-02168059Test

المؤلفون: Pascal Wolter, Alexandra Karadimou, Jean-Jacques Body, Patrick Schöffski, H. Van Poppel, Ludo Willems, Benoit Beuselinck, Philip R. Debruyne, Annick Rogiers, T. van Cann, R. Elaidi, Robert Paridaens, Herlinde Dumez, Joost Berkers, Evelyne Lerut

المصدر: British Journal of Cancer
British Journal of Cancer, 107 (10

مصطلحات موضوعية: Male, Cancer Research, Pathology, Diphosphonates -- administration & dosage -- adverse effects, Indoles, Phenylurea Compounds -- administration & dosage, Antineoplastic Combined Chemotherapy Protocols -- adverse effects -- therapeutic use, Targeted therapy, bone metastases, Renal cell carcinoma, Antineoplastic Combined Chemotherapy Protocols, Bone Density Conservation Agents -- administration & dosage -- adverse effects, Bone Neoplasms -- drug therapy -- pathology -- secondary, Sunitinib, Neoplasm Metastasis, Indoles -- administration & dosage, Outcome, Bone Density Conservation Agents, Diphosphonates, Protein Kinase Inhibitors -- administration & dosage, Osteonecrosis, Bisphosphonates, Sciences bio-médicales et agricoles, Middle Aged, Protein-Tyrosine Kinases, Sorafenib, Prognosis, targeted therapy, Kidney Neoplasms, Treatment Outcome, Oncology, outcome, Female, Niacinamide -- administration & dosage -- analogs & derivatives, Tyrosine kinase, medicine.drug, Carcinoma, Renal Cell -- drug therapy -- pathology -- secondary, Niacinamide, medicine.medical_specialty, renal cell carcinoma, Bone Neoplasms, Osteonecrosis -- chemically induced, Disease-Free Survival, Kidney Neoplasms -- drug therapy -- pathology, Pyrroles -- administration & dosage, medicine, Carcinoma, Humans, Pyrroles, Carcinoma, Renal Cell, Protein Kinase Inhibitors, bisphosphonates, Retrospective Studies, Osteonecrosis of the jaw, business.industry, Protein-Tyrosine Kinases -- antagonists & inhibitors, Bone metastases, Phenylurea Compounds, medicine.disease, osteonecrosis of the jaw, Concomitant, Cancer research, Clinical Study, business

الوصف: The presence of bone metastases in patients with metastatic renal cell carcinoma treated with oral tyrosine kinase inhibitors (TKIs) is associated with poorer outcome as compared with patients without bone involvement. Concomitant bisphosphonates could probably improve outcomes but also induce osteonecrosis of the jaw (ONJ).
Journal Article
Research Support, Non-U.S. Gov't
SCOPUS: ar.j
info:eu-repo/semantics/published

وصف الملف: 1 full-text file(s): application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cdb22c4137af4f142fa2a48d0882b042Test
https://pubmed.ncbi.nlm.nih.gov/23132391Test