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Tracy L Stockley, Amit M Oza, Hal K Berman, Natasha B Leighl, Jennifer J Knox, Frances A Shepherd, Eric X Chen, Monika K Krzyzanowska, Neesha Dhani, Anthony M Joshua, Ming-Sound Tsao, Stefano Serra, Blaise Clarke, Michael H Roehrl, Tong Zhang, Mahadeo A Sukhai, Nadia Califaretti, Mateya Trinkaus, Patricia Shaw, Theodorus van der Kwast, Lisa Wang, Carl Virtanen, Raymond H Kim, Albiruni R A Razak, Aaron R Hansen, Celeste Yu, Trevor J Pugh, Suzanne Kamel-Reid, Lillian L Siu, Philippe L Bedard
BACKGROUND: The clinical utility of molecular profiling of tumor tissue to guide treatment of patients with advanced solid tumors is unknown. Our objectives were to evaluate the frequency of genomic alterations, clinical "actionability" of somatic variants, enrollment in mutation-targeted or other clinical trials, and outcome of molecular profiling for advanced solid tumor patients at the Princess Margaret Cancer Centre (PM). METHODS: Patients with advanced solid tumors aged ≥18 years, good performance status, and archival tumor tissue available were prospectively consented...
October 25, 2016: Genome Medicine
Zhiwei Sun, Xicheng Wang, Jun Jia, Chuanling Liu, Xiaodong Zhang, Lin Shen
OBJECTIVE: To analyze the relationship between primary tumor location and clinical response of chemotherapy in patients with metastatic colorectal cancer(mCRC). METHODS: Clinical data of 721 mCRC patients who received first-line and second-line chemotherapy in Peking University Cancer Hospital between January 1996 and December 2011 were collected. All the patients were divided into 5 groups according to primary tumor location: ileocecum in 61 patients(8.5%), ascending colon or hepatic flexure in 126 patients (17...
October 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
Mohamed Bouchahda, Valérie Boige, Denis Smith, Abdoulaye Karaboué, Michel Ducreux, Mohamed Hebbar, Céline Lepère, Christian Focan, Rosine Guimbaud, Pasquale Innominato, Sameh Awad, Carlos Carvalho, Salvatore Tumolo, Stephanie Truant, Thierry De Baere, Denis Castaing, Philippe Rougier, Jean-François Morère, Julien Taieb, René Adam, Francis Lévi
BACKGROUND: Early tumour shrinkage has been associated with improved survival in patients receiving cetuximab-based systemic chemotherapy for liver metastases from colorectal cancer (LM-CRC). We tested this hypothesis for previously treated LM-CRC patients receiving cetuximab (500 mg/m(2)) and triplet hepatic artery infusion (HAI) within European trial OPTILIV. METHODS: Irinotecan (180 mg/m(2)), 5-fluorouracil (2800 mg/m(2)) and oxaliplatin (85 mg/m(2)) were given as chronomodulated or conventional delivery...
October 17, 2016: European Journal of Cancer
Dengxia Yang, Gavitt Woodard, Chan Zhou, Xinyue Wang, Zhujun Liu, Zhaoxiang Ye, Kai Li
BACKGROUND: Certain radiographic signs of a treatment response, such as cavitation, changes in density, or tumor change along a short axis, are not considered by Response Evaluation Criteria in Solid Tumors (RECIST). This study evaluates what additional prognostic information can be obtained by including these criteria in tumor assessment. METHODS: Data of 105 patients were included. Tumor cavitation was observed in 51 patients at baseline. An additional 23 patients developed tumor cavitation during treatment...
September 2016: Thoracic Cancer
Antonin Levy, Christophe Massard, Jean-Charles Soria, Eric Deutsch
PURPOSE: To assess preliminary safety and efficacy results of the anti-programmed cell death ligand-1 (anti-PD-L1) durvalumab in combination with radiotherapy (RT) in an expansion cohort of patients included in a phase 1/2 trial at our institution. PATIENTS AND METHODS: Data from patients who received concurrent palliative RT with durvalumab (10 mg/kg every 2 weeks via intravenous infusion) were analysed in terms of safety (CTCAE v4.0) and efficacy (RECIST v1.1 and tumour growth rate [TGR])...
October 17, 2016: European Journal of Cancer
Yoichi Kato
We assessed the efficacy of WT1 class I peptide and WT1 class II peptide pulsed dendritic cell(DC)therapy for a wide range of advanced cancers. This retrospective study included 60 advanced cancer patients who were vaccinated 5times or more in this clinic between September 2013 and December 2015. The clinical response was examined. This treatment was approved by the ethics panel at this institution. Sixty patients were injected an average of 6.15times with dendritic cells(DCs) (2.6×10 / 7 cells/injection)...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Yang Luo, Junling Li, Yan Wang, Xuezhi Hao, Fenglian Qu
BACKGROUND: Epidermal growth factor receptor (EGFR) is commonly overexpressed in lung squamous cell carcinoma and has been associated with impaired prognosis. The aim of this study was to observe the efficacy and safety of nimotuzumab, a anti-EGFR monoclonal antibody, combined with chemotherapy as second- or later-line in the treatment of advanced lung squamous cell carcinoma. METHODS: A retrospective analysis of clinical data was conducted in 13 patients with advanced lung squamous cell carcinoma, who were administered with nimotuzumab combined with chemotherapy as second-line or later-line treatment...
October 20, 2016: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
Troels Holz Borch, Lotte Engell-Noerregaard, Trine Zeeberg Iversen, Eva Ellebaek, Özcan Met, Morten Hansen, Mads Hald Andersen, Per Thor Straten, Inge Marie Svane
INTRODUCTION: Vaccination with dendritic cells (DCs) has generally not fulfilled its promise in cancer immunotherapy due to ineffective translation of immune responses into clinical responses. A proposed reason for this is intrinsic immune regulatory mechanisms, such as regulatory T cells (Tregs). A metronomic regimen of cyclophosphamide (mCy) has been shown to selectively deplete Tregs. To test this in a clinical setting, we conducted a phase I trial to evaluate the feasibility and safety of vaccination with DCs transfected with mRNA in combination with mCy in patients with metastatic malignant melanoma (MM)...
2016: Oncoimmunology
Olivier Mir, Thomas Brodowicz, Antoine Italiano, Jennifer Wallet, Jean-Yves Blay, François Bertucci, Christine Chevreau, Sophie Piperno-Neumann, Emmanuelle Bompas, Sébastien Salas, Christophe Perrin, Corinne Delcambre, Bernadette Liegl-Atzwanger, Maud Toulmonde, Sarah Dumont, Isabelle Ray-Coquard, Stéphanie Clisant, Sophie Taieb, Cécile Guillemet, Maria Rios, Olivier Collard, Laurence Bozec, Didier Cupissol, Esma Saada-Bouzid, Christine Lemaignan, Wolfgang Eisterer, Nicolas Isambert, Loïc Chaigneau, Axel Le Cesne, Nicolas Penel
BACKGROUND: Regorafenib is a multikinase inhibitor with proven activity in refractory gastrointestinal stromal tumours and chemotherapy-refractory advanced colorectal cancers. We assessed this agent's efficacy and safety in patients with metastatic soft tissue sarcomas previously treated with anthracycline. METHODS: In this randomised, double-blind, phase 2 trial undertaken in France and Austria, we enrolled patients aged 18 years and older with advanced soft tissue sarcomas who had received previous doxorubicin or other anthracycline treatment...
October 14, 2016: Lancet Oncology
Magdalena Lukamowicz-Rajska, Christiane Mittmann, Michael Prummer, Qing Zhong, Jens Bedke, Jörg Hennenlotter, Arnulf Stenzl, Axel Mischo, Svenja Bihr, Manuela Schmidinger, Ursula Vogl, Iris Blume, Christoph Karlo, Peter Schraml, Holger Moch
A number of treatments targeting VEGF or mTOR pathways have been approved for metastatic clear cell Renal Cell Carcinoma (ccRCC), but the majority of patients show disease progression after first line therapy with a very low rate of complete or long-term responders. It has been shown that miRs may play a role in prediction of treatment response in various cancer types. The aim of our study was to identify a miR signature predictive for RCC patients' response to antiangiogenic tyrosine kinase inhibitor (TKI) treatment in the first line therapy...
October 12, 2016: Oncotarget
Thomas W Lycan, Timothy S Pardee, William J Petty, Marcelo Bonomi, Angela Alistar, Zanetta S Lamar, Scott Isom, Michael D Chan, Antonius A Miller, Jimmy Ruiz
BACKGROUND: Small cell lung cancer (SCLC) is a common lung cancer which presents with extensive stage disease at time of diagnosis in two-thirds of patients. For treatment of advanced disease, traditional platinum doublet chemotherapy induces response rates up to 80% but with few durable responses. CPI-613 is a novel anti-cancer agent that selectively inhibits the altered form of mitochondrial energy metabolism in tumor cells. METHODS: We evaluated CPI-613 with a single-arm, open-label phase II study in patients with relapsed or refractory SCLC...
2016: PloS One
David S Hong, Van K Morris, Badi El Osta, Alexey V Sorokin, Filip Janku, Siqing Fu, Michael J Overman, Sarina Piha-Paul, Vivek Subbiah, Bryan Kee, Apostolia Tsimberidou, David Fogelman, Jorge Bellido, Imad Shureiqi, Helen Huang, Johnique Atkins, Gabi Tarcic, Nicolas Sommer, Richard Lanman, Funda Meric-Bernstam, Scott Kopetz
In vitro, EGFR inhibition, combined with the BRAF inhibitor vemurafenib, causes synergistic cytotoxicity for BRAFV600E metastatic colorectal cancer (mCRC), further augmented by irinotecan. The safety and efficacy of vemurafenib, irinotecan, and cetuximab in BRAF-mutated malignancies are not defined. In this 3+3 phase I study, patients with BRAFV600E advanced solid cancers received cetuximab and irinotecan with escalating doses of vemurafenib. Nineteen patients (18 with mCRC, 1 with appendiceal cancer) were enrolled...
October 11, 2016: Cancer Discovery
David Propper, Keith Jones, D Alan Anthoney, Wasat Mansoor, Daniel Ford, Martin Eatock, Roshan Agarwal, Michiyasu Inatani, Tomohisa Saito, Masaichi Abe, T R Jeffry Evans
BACKGROUND: TP300, a recently developed synthetic camptothecin analogue, is a highly selective topoisomerase I inhibitor. A phase I study showed good safety and tolerability. As camptothecins have proven active in oesophago-gastric adenocarcinomas, in this phase II study we assessed the efficacy and safety of TP300 in patients with gastric or gastro-oesophageal junction (GOJ) adenocarcinomas. METHODS: Eligible patients had metastatic or locally advanced gastric or Siewert Types II or III GOJ inoperable adenocarcinoma...
October 10, 2016: BMC Cancer
Eiso Hiyama, Tomoro Hishiki, Kenichiro Watanabe, Kohmei Ida, Michihiro Yano, Takaharu Oue, Tomoko Iehara, Ken Hoshino, Katsuyoshi Koh, Yukichi Tanaka, Sho Kurihara, Yuka Ueda, Yoshiyuki Onitake
BACKGROUND/PURPOSE: We aimed to clarify whether surgical resectability and tumor response after preoperative chemotherapy (preCTx) represented prognostic factors for patients with hepatoblastoma (HBL) in the JPLT-2 study (1999-2012). METHODS: Patients (N=342) with HBL who underwent preCTx were eligible. PRETEXT, CHIC risk stratification (standard [SR], intermediate [IR] and high risk [HR]) at diagnosis, POST-TEXT, and tumor resectability were evaluated by imaging...
September 17, 2016: Journal of Pediatric Surgery
Fedor V Moiseyenko, Vladimir M Moiseyenko, Svetlana N Aleksakhina, Vyacheslav A Chubenko, Nikita M Volkov, Kseniya S Kozyreva, Michail M Kramchaninov, Alexandr S Zhuravlev, Kseniya V Shelekhova, Alexandr O Ivantsov, Aigul R Venina, Elena V Preobrazhenskaya, Natalia V Mitiushkina, Aglaya G Iyevleva, Evgeny N Imyanitov
BACKGROUND: Discontinuation of gefitinib treatment is often accompanied by a disease flare. Some studies have demonstrated a benefit of the use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) beyond progression; however, long-term results of these investigations remain limited. PATIENTS AND METHODS: We observed 70 patients with EGFR-mutated (EGFR-M+) non-small cell lung cancer (NSCLC) receiving single-agent gefitinib in a routine clinical setting; 56 patients were experiencing RECIST progression at the time of the analysis...
2016: Oncology Research and Treatment
Giulia Pasquini, Enrico Vasile, Chiara Caparello, Caterina Vivaldi, Gianna Musettini, Monica Lencioni, Iacopo Petrini, Lorenzo Fornaro, Alfredo Falcone
PURPOSE: The aim of this study was to evaluate the activity of the combination of 5-fluorouracil/folinic acid and irinotecan (FOLFIRI) as third-line chemotherapy (CT) in metastatic gastric cancer (mGC) patients pretreated with platinum derivatives, fluoropyrimidines, and taxanes. METHODS: We prospectively collected data of mGC patients treated with third-line FOLFIRI at our institution from 2009 to 2014. Eligible patients should be treated with a fluoropyrimidine-platinum first-line CT and a subsequent taxane-based second-line CT...
October 6, 2016: Oncology
Leila Khoja, Minnie Kibiro, Ur Metser, Craig Gedye, David Hogg, Marcus O Butler, Eshetu G Atenafu, Anthony M Joshua
BACKGROUND: Radiological assessment of response to checkpoint inhibitors remains imperfect. We evaluated individual lesion and inter-patient response by response evaluation (RECIST) 1.1, immune-related response criteria (irRC), CHOI and modified CHOI (mCHOI) and correlated response with overall survival (OS). METHODS: Thirty-seven patients with 567 measurable lesions treated with pembrolizumab in the Keynote 001 trial were studied. Association of response with OS was determined...
October 4, 2016: British Journal of Cancer
E Coche
Lung tumor response to therapy may be evaluated in most instances by morphological criteria such as RECIST 1.1 on computed tomography (CT) or magnetic resonance imaging (MRI). However, those criteria are limited because they are based on tumoral dimensional changes and do not take into account other morphologic criteria such as density evaluation, functional or metabolic changes that may occur following conventional or targeted chemotherapy. New techniques such as dual-energy CT, PET-CT, MRI including diffusion-weighted MRI has to be considered into the new technical armamentarium for tumor response evaluation...
October 2016: Diagnostic and Interventional Imaging
F Husseini, J-P Delord, C Fournel-Federico, J Guitton, P Erbs, M Homerin, C Halluard, C Jemming, C Orange, J-M Limacher, J-E Kurtz
BACKGROUND: TG4023 is a modified vaccinia virus Ankara (MVA) containing the yeast-originated transgene FCU1, expressing cytosine deaminase and uracil phosphoribosyltransferase enzymes that transform the prodrug flucytosine (5-FC) into cytotoxic 5-fluorouracil (5-FU) and 5-fluorouridine-5'-monophosphate (5-FUMP), respectively. This first-in-human study aimed to assess the maximum tolerated dose (MTD) of intra-tumoral (IT) TG4023 and the safety, feasibility, and proof-of-concept (PoC) of TG4023/5-FC combination to deliver high 5-FU concentrations in tumors...
September 29, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Wolfgang P Fendler, Svenja Reinhardt, Harun Ilhan, Andreas Delker, Guido Böning, Franz J Gildehaus, Christian Stief, Peter Bartenstein, Christian Gratzke, Sebastian Lehner, Axel Rominger
Prostate cancer can be targeted by ligands to the prostate-specific membrane antigen (PSMA). We aimed to evaluate dosimetry, safety and efficacy of 177Lu-PSMA-617 radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC).Fifteen patients each received two cycles of 3.7 GBq (n = 5) or 6.0 GBq (n = 10) 177Lu-PSMA-617 at an eight to ten weeks interval. For safety monitoring, each treatment was followed by dosimetry with serial quantitative SPECT as well as inpatient and outpatient recording of adverse events...
September 24, 2016: Oncotarget
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