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European Journal of Cancer

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https://www.readbyqxmd.com/read/28324751/the-rationale-of-indoleamine-2-3-dioxygenase-inhibition-for-cancer-therapy
#1
REVIEW
Lieve Brochez, Ines Chevolet, Vibeke Kruse
Indoleamine 2,3-dioxygenase (IDO, also referred to as IDO1) has been demonstrated to be a normal endogenous mechanism of acquired peripheral immune tolerance in vivo. In the field of oncology, IDO expression and/or activity has been observed in several cancer types and has usually been associated with negative prognostic factors and worse outcome measures. This manuscript reviews current available data on the role of IDO in cancer and the current results obtained with IDO inhibition, both in animal models and in phase 1 and 2 clinical trials in humans...
March 18, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28324750/biological-mechanisms-of-immune-escape-and-implications-for-immunotherapy-in-head-and-neck-squamous-cell-carcinoma
#2
REVIEW
Jennifer D Moy, Jessica M Moskovitz, Robert L Ferris
Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with high morbidity and mortality. Despite advances in cytotoxic therapies and surgical techniques, overall survival (OS) has not improved over the past few decades. This emphasises the need for intense investigation into novel therapies with good tumour control and minimal toxicity. Cancer immunotherapy has led this endeavour, attempting to improve tumour recognition and expand immune responses against tumour cells. While various forms of HNSCC immunotherapy are in preclinical trials, the most promising direction thus far has been with monoclonal antibodies (mAbs), targeting growth factor and immune checkpoint receptors...
March 18, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28324749/a-phase-i-study-of-sar405838-a-novel-human-double-minute-2-hdm2-antagonist-in-patients-with-solid-tumours
#3
Maja de Jonge, Vincent A de Weger, Mark A Dickson, Marlies Langenberg, Axel Le Cesne, Andrew J Wagner, Karl Hsu, Wei Zheng, Sandrine Macé, Gilles Tuffal, Koruth Thomas, Jan H M Schellens
PURPOSE: In tumours with wild-type TP53, the tumour-suppressive function of p53 is frequently inhibited by HDM2. This phase I, dose-escalating study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics and pharmacodynamics of SAR405838, an HDM2 inhibitor, in patients with advanced solid tumours (NCT01636479). METHODS: In dose escalation, patients with any locally advanced/metastatic solid tumour with TP53 mutation prevalence below 40%, or documented as TP53 wild-type, were eligible...
March 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28324748/influenza-vaccination-in-adult-patients-with-solid-tumours-treated-with-chemotherapy
#4
REVIEW
Albert Vollaard, Imke Schreuder, Lizzy Slok-Raijmakers, Wim Opstelten, Guus Rimmelzwaan, Hans Gelderblom
Patients with solid tumours receiving chemotherapy are at risk for influenza complications. Yearly influenza vaccination is recommended to patients treated with chemotherapy. However, adherence to vaccination is low, most likely due to lack of data on efficacy, optimal timing and safety of vaccination. There is scarce evidence for the effectiveness of the influenza vaccine in adult patients with solid tumours and chemotherapy on reduction of pneumonia, decreased mortality and fewer interruptions of oncological treatment...
March 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28324747/optimal-dose-reduction-of-folfirinox-for-preserving-tumour-response-in-advanced-pancreatic-cancer-using-cumulative-relative-dose-intensity
#5
Jong-Chan Lee, Jin Won Kim, Soyeon Ahn, Hyoung Woo Kim, Jongchan Lee, Young Hoon Kim, Kyu-Hyun Paik, Jaihwan Kim, Jin-Hyeok Hwang
BACKGROUND: FOLFIRINOX has increased efficacy but also toxicity. Despite various modified FOLFIRINOX regimens, how much reduction is acceptable remains unclear. This study aimed to find the optimal relative dose intensity (RDI, %) of FOLFIRINOX that preserves tumour responses in patients with advanced pancreatic cancer (PC). METHODS: We reviewed 201 patients with PC treated with first-line FOLFIRINOX during 2012-2015. We established a modified Hryniuk model (http://www...
March 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28324746/denosumab-in-advanced-unresectable-giant-cell-tumour-of-bone-gctb-for-how-long
#6
E Palmerini, N S Chawla, S Ferrari, M Sudan, P Picci, E Marchesi, M Piccinni Leopardi, I Syed, K K Sankhala, P Parthasarathy, W E Mendanha, M Pierini, A Paioli, S P Chawla
BACKGROUND: Giant-cell tumours of bone (GCTB) are RANK/RANK-ligand (RANKL) positive, aggressive and progressive osteolytic tumours. Denosumab, a RANKL inhibitor, was FDA-approved for adults and skeletally mature adolescents with unresectable GCTB or when surgical resection is likely to result in severe morbidity. Data on long-term toxicity and activity of denosumab monthly 'GCTB-schedule' (120 mg per 12/year, 1440 mg total dose/year) are lacking. METHODS: Patients with GCTB receiving denosumab, 120 mg on days 1, 8, 15, 29 and every 4 weeks thereafter, from 2006 to 2015 treated in two centres were included...
March 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28301826/a-multicenter-phase-ii-study-of-sunitinib-in-patients-with-locally-advanced-or-metastatic-differentiated-anaplastic-or-medullary-thyroid-carcinomas-mature-data-from-the-thysu-study
#7
Alain Ravaud, Christelle de la Fouchardière, Philippe Caron, Adelaïde Doussau, Christine Do Cao, Julien Asselineau, Patrice Rodien, Damien Pouessel, Patricia Nicolli-Sire, Marc Klein, Claire Bournaud-Salinas, Jean-Louis Wemeau, Anne Gimbert, Marie-Quitterie Picat, Delphine Pedenon, Laurence Digue, Amaury Daste, Bogdan Catargi, Jean-Pierre Delord
PURPOSE: Patients with advanced radioactive iodine resistant differentiated (MDTC) or medullary (MMTC) thyroid cancer had an unmet need. Early data showed promising efficacy of vascular endothelial growth factor receptor inhibitors. We investigated sunitinib in this setting. PATIENTS AND METHODS: This phase 2 trial enrolled MDTC, anaplastic (MATC) and MMTC patients in 1st line anti-angiogenic therapy with sunitinib at 50 mg/d, 4/6w. Objective response rate was the primary end-point...
March 13, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28292559/pathological-characterisation-of-male-breast-cancer-results-of-the-eortc-10085-tbcrc-big-nabcg-international-male-breast-cancer-program
#8
Marijn A Vermeulen, Leen Slaets, Fatima Cardoso, Sharon H Giordano, Konstantinos Tryfonidis, Paul J van Diest, Nizet H Dijkstra, Carolien P Schröder, Christi J van Asperen, Barbro Linderholm, Kim Benstead, Renee Foekens, John W M Martens, John M S Bartlett, Carolien H M van Deurzen
AIM: Several prognostic histological features have been established in female breast cancer (BC), but it is unknown whether these can be extrapolated to male BC patients. The aim of this study was to evaluate the prognostic value of several histological features in a large series of male BC. METHODS: Central pathology review was performed for 1483 male BCs collected through part 1 of the European Organisation for Research and Treatment of Cancer (EORTC) International Male BC Program...
March 11, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28286287/incidence-of-capecitabine-related-cardiotoxicity-in-different-treatment-schedules-of-metastatic-colorectal-cancer-a-retrospective-analysis-of-the-cairo-studies-of-the-dutch-colorectal-cancer-group
#9
Johannes J M Kwakman, Lieke H J Simkens, Linda Mol, Wouter E M Kok, Miriam Koopman, Cornelis J A Punt
BACKGROUND: The frequency of capecitabine-related cardiotoxicity has been reported to be low but includes serious adverse events. We conducted a retrospective analysis of the incidence and severity of capecitabine-related cardiotoxicity in different regimens in the treatment of metastatic colorectal cancer in three randomised phase 3 studies. METHODS: We used data of cardiac events reported in the CAIRO, CAIRO2 and CAIRO3 studies of the Dutch Colorectal Cancer Group (DCCG) and analysed the incidence and severity of cardiac events in the different treatment regimens of the trials which all included the use of capecitabine...
March 9, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28286286/cancer-immunotherapy-targeting-the-cd47-sirp%C3%AE-axis
#10
REVIEW
Kipp Weiskopf
The success of cancer immunotherapy has generated tremendous interest in identifying new immunotherapeutic targets. To date, the majority of therapies have focussed on stimulating the adaptive immune system to attack cancer, including agents targeting CTLA-4 and the PD-1/PD-L1 axis. However, macrophages and other myeloid immune cells offer much promise as effectors of cancer immunotherapy. The CD47/signal regulatory protein alpha (SIRPα) axis is a critical regulator of myeloid cell activation and serves a broader role as a myeloid-specific immune checkpoint...
March 9, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28284173/patient-derived-solitary-fibrous-tumour-xenografts-predict-high-sensitivity-to-doxorubicin-dacarbazine-combination-confirmed-in-the-clinic-and-highlight-the-potential-effectiveness-of-trabectedin-or-eribulin-against-this-tumour
#11
S Stacchiotti, M Saponara, R Frapolli, M Tortoreto, D Cominetti, S Provenzano, T Negri, G P Dagrada, A Gronchi, C Colombo, B Vincenzi, G Badalamenti, V Zuco, S L Renne, P Collini, C Morosi, A P Dei Tos, E Bello, S Pilotti, P G Casali, M D'Incalci, N Zaffaroni
BACKGROUND: Preclinical models that mimic pathological and molecular features of solitary fibrous tumour (SFT) represent an important tool to select effective regimes and novel compounds to be tested in the clinic. This study was aimed at developing two preclinical models of SFT, assessing their predictive value in the clinic and selecting potential novel effective treatments. MATERIAL AND METHODS: Two dedifferentiated-SFT (D-SFT) models obtained from patients' biopsies were grown in immunodeficient mice...
March 8, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28284172/clinical-characteristics-and-treatment-outcome-in-a-large-multicentre-observational-cohort-of-pdgfra-exon-18-mutated-gastrointestinal-stromal-tumour%C3%A2-patients
#12
Sheima Farag, Neeta Somaiah, Haesun Choi, Birthe Heeres, Wei-Lien Wang, Hester van Boven, Petra Nederlof, Robert Benjamin, Winette van der Graaf, Dirk Grunhagen, Pieter Boonstra, Anna K L Reyners, Hans Gelderblom, Neeltje Steeghs
PURPOSE: Patients, platelet-derived growth factor receptor alpha (PDGFRA) D842V-mutated gastrointestinal stromal tumours (GISTs) are known for their insensitivity to imatinib. However, in clinical practice responses have been observed in some patients. We describe the natural history and treatment outcomes in a cohort of PDGFRA exon 18 mutated GIST patients. PATIENTS AND METHODS: A retrospective cohort study was conducted in PDGFRA exon 18 mutation GIST patients treated in six expert centres in the Netherlands and the United States...
March 8, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28284171/molecular-subtypes-of-metastatic-colorectal-cancer-are-associated-with-patient-response-to-irinotecan-based-therapies
#13
M Del Rio, C Mollevi, F Bibeau, N Vie, J Selves, J-F Emile, P Roger, C Gongora, J Robert, N Tubiana-Mathieu, M Ychou, P Martineau
BACKGROUND: Currently, metastatic colorectal cancer is treated as a homogeneous disease and only RAS mutational status has been approved as a negative predictive factor in patients treated with cetuximab. The aim of this study was to evaluate if recently identified molecular subtypes of colon cancer are associated with response of metastatic patients to first-line therapy. PATIENTS AND METHODS: We collected and analysed 143 samples of human colorectal tumours with complete clinical annotations, including the response to treatment...
March 8, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28283351/corrigendum-to-predicting-and-preventing-thromboembolic-events-in-patients-receiving-cisplatin-based-chemotherapy-for-germ-cell-tumours-eur-j-cancer-69-2016-151-157
#14
Marco Gizzi, Lucie Oberic, Christophe Massard, Audrey Poterie, Gwenael Le Teuff, Yohann Loriot, Laurence Albiges, Giulia Baciarello, Judith Michels, Alberto Bossi, Pierre Blanchard, Bernard Escudier, Karim Fizazi
No abstract text is available yet for this article.
March 7, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28282612/imatinib-induces-sustained-progression-arrest-in-recist-progressive-desmoid-tumours-final-results-of-a-phase-ii-study-of-the-german-interdisciplinary-sarcoma-group-gisg
#15
Bernd Kasper, Viktor Gruenwald, Peter Reichardt, Sebastian Bauer, Geraldine Rauch, Ronald Limprecht, Michaela Sommer, Antonia Dimitrakopoulou-Strauss, Lothar Pilz, Florian Haller, Peter Hohenberger
BACKGROUND: Desmoid tumours describe a rare monoclonal, fibroblastic proliferation characterised by an often unpredictable clinical course. Surgery is one therapeutic option for progressing patients, except if mutilating and associated with considerable function loss. Different systemic treatment approaches have been investigated and promising results could be demonstrated using imatinib. PATIENTS AND METHODS: We initiated a phase II trial within the German Interdisciplinary Sarcoma Group (GISG) evaluating imatinib to induce progression arrest in desmoid tumour patients being Response Evaluation Criteria in Solid Tumours (RECIST) progressive, not amenable to surgical resection with R0 intent or accompanied by unacceptable function loss (NCT01137916)...
March 7, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28279941/long-term-outcome-of-the-remagus-02-trial-a-multicenter-randomised-phase-ii-trial-in-locally-advanced-breast-cancer%C3%A2-patients-treated-with-neoadjuvant-chemotherapy-with-or-without-celecoxib-or-trastuzumab-according-to-her2-status
#16
Sylvie Giacchetti, Anne-Sophie Hamy, Suzette Delaloge, Etienne Brain, Frédérique Berger, Brigitte Sigal-Zafrani, Marie-Christine Mathieu, Philippe Bertheau, Jean Marc Guinebretière, Mahasti Saghatchian, Florence Lerebours, Chafouny Mazouni, Olivier Tembo, Marc Espié, Fabien Reyal, Michel Marty, Bernard Asselain, Jean-Yves Pierga
BACKGROUND: The REMAGUS-02 multicenter randomised phase II trial showed that the addition to neoadjuvant chemotherapy (NAC) of trastuzumab in patients with localised HER2-positive breast cancer (BC) increased the pathological complete response (pCR) rate and that the addition of celecoxib in HER2-negative cases did not increase the pCR rate. We report here the long-term follow-up results for disease-free survival (DFS) and overall survival (OS). PATIENTS AND METHODS: From 2004 to 2007, 340 stage II-III BC patients were randomly assigned to receive neoadjuvant EC-T (four cycles of epirubicin-cyclophosphamide followed by four cycles of docetaxel) +/- celecoxib in HER2-negative cases (n = 220) and ± trastuzumab in HER2-positive cases (n = 120)...
March 6, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28273485/clinical-factors-of-response-in-patients-with-advanced-ovarian-cancer-participating-in-early-phase-clinical-trials
#17
Angela George, Rebecca Kristeleit, Saeed Rafii, Caroline O Michie, Rebecca Bowen, Vasiliki Michalarea, Tom van Hagen, Mabel Wong, Grigorios Rallis, L Rhoda Molife, Juanita Lopez, Udai Banerji, Susana N Banerjee, Martin E Gore, Johann S de Bono, Stan B Kaye, Timothy A Yap
Drug resistance to conventional anticancer therapies is almost inevitable in patients with advanced ovarian cancer (AOC), limiting their available treatment options. Novel phase I trial therapies within a dedicated drug development unit may represent a viable alternative; however, there is currently little evidence for patient outcomes in such patients. To address this, we undertook a retrospective review of patients with AOC allocated to phase I trials in the Drug Development Unit at Royal Marsden Hospital (RMH) between June 1998 and October 2010...
March 5, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28282611/phase-ib-dose-finding-study-of-abiraterone-acetate-plus-buparlisib-bkm120-or-dactolisib-bez235-in-patients-with-castration-resistant-prostate-cancer
#18
Christophe Massard, Kim Nguyen Chi, Daniel Castellano, Johann de Bono, Gwenaelle Gravis, Luc Dirix, Jean-Pascal Machiels, Alain Mita, Begona Mellado Gonzalez, Sabine Turri, Joan Maier, Denes Csonka, Arunava Chakravartty, Karim Fizazi
BACKGROUND: The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signalling axis and androgen receptor (AR) pathways exhibit reciprocal feedback regulation in phosphatase and tensin homologue (PTEN)-deficient metastatic castration-resistant prostate cancer (CRPC) in preclinical models. This phase Ib study evaluated the pan-PI3K inhibitor buparlisib (BKM120) and the dual pan-PI3K/ mammalian target of rapamycin (mTOR) inhibitor dactolisib (BEZ235) in combination with abiraterone acetate (AA) in patients with CRPC...
March 3, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28267657/preoperative-radiotherapy-in-breast-cancer-patients-32%C3%A2-years-of-follow-up
#19
F G Riet, F Fayard, R Arriagada, M A Santos, C Bourgier, M Ferchiou, S Heymann, S Delaloge, C Mazouni, A Dunant, S Rivera
This study evaluates the long-term outcomes of a retrospective cohort of breast cancer (BC) patients who had received curatively intended premastectomy radiation therapy (RT). We analysed locoregional control, disease-free survival (DFS) and overall survival (OS), pathological complete remission (pCR), predictors thereof, and immediate safety. The series consisted of 187 patients with a median age of 49 years [43-60] and T2-T4 or N2 tumours. Between 1970 and 1984, they had received slightly hypofractionated RT to the whole breast, ipsilateral supraclavicular fossa and axilla ± the internal mammary chain (45-55 Gy/18 fractions of 2...
March 3, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28264791/more-than-5000-patients-with-metastatic-melanoma-in-europe-per-year-do-not-have-access-to-recommended-first-line-innovative-treatments
#20
L Kandolf Sekulovic, K Peris, A Hauschild, A Stratigos, J-J Grob, P Nathan, R Dummer, A-M Forsea, C Hoeller, H Gogas, L Demidov, C Lebbe, C Blank, J Olah, L Bastholt, D Herceg, B Neyns, R Vieira, J Hansson, P Rutkowski, I Krajsova, M Bylaite-Bucinskiene, I Zalaudek, J Maric-Brozic, N Babovic, M Banjin, K Putnik, G Weinlich, V Todorovic, K Kirov, J Ocvirk, A Zhukavets, M Kukushkina, L De La Cruz Merino, A Ymeri, M Risteski, C Garbe
BACKGROUND: Despite the efficacy of innovative treatments for metastatic melanoma, their high costs has led to disparities in cancer care among different European countries. We analysed the availability of these innovative therapies in Europe and estimated the number of patients without access to first-line recommended treatment per current guidelines of professional entities such as the European Society for Medical Oncology (ESMO), the European Organisation for Research and Treatment of Cancer (EORTC), the European Association of Dermato-Oncology (EADO), and European Dermatology Forum (EDF)...
March 2, 2017: European Journal of Cancer
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