Menée à partir de données portant sur 163 patients atteints d'un adénocarcinome mucineux appendiculaire, cette étude multicentrique montre qu'une chimiothérapie hyperthermique intrapéritonéale après une chirurgie cytoréductive améliore la survie des patients

Hyperthermic Intraperitoneal Chemotherapy Following Cytoreductive Surgery Improves Outcome in Patients With Primary Appendiceal Mucinous Adenocarcinoma: A Pooled Analysis From Three Tertiary Care Centers

Shaib, Walid L. ; Martin, Ludmila Katherine ; Choi, Minsing ; Chen, Zhengjia ; Krishna, Kavya ; Kim, Sungjin ; Brutcher, Edith ; Staley, Charles ; Maithel, Shishir K. ; Philip, Philip ; Abdel-Misih, Sherif ; Bekaii-Saab, Tanios S. ; El-Rayes, Bassel F.

Appendiceal mucinous neoplasms (AMN) are a rare heterogeneous group of diseases. In the absence of randomized trials, AMN management is controversial. The goal of this study was to evaluate the impact of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery on survival in AMN patients.Patient data including demographics, pathology, type of therapy, and outcomes were collected from Emory University, the Ohio State University, and Wayne State University databases. One of [...]

Menée sur 299 patients présentant des métastases spinales traitées par rayonnements ionisants, cette étude analyse le rôle d'une radiothérapie palliative à fraction unique et du niveau d'instabilité de la colonne vertébrale associé à la lésion tumorale dans la survenue d'événements rachidiens indésirables

Adverse Outcomes after Palliative Radiation Therapy for Uncomplicated Spine Metastases: Role of Spinal Instability and Single Fraction Radiation Therapy

Lam, Tai-Chung ; Uno, Hajime ; Krishnan, Monica ; Lutz, Steven ; Groff, Michael ; Cheney, Matthew ; Balboni, Tracy

Background : Level I evidence demonstrates equivalent pain response after single fraction (SF) or multiple fraction (MF) radiation therapy (RT) for bone metastases. There are little data to inform incidence and predictors of adverse outcomes after RT for spine metastases. Methods : At a single institution, 299 uncomplicated spine metastases (without cord compression, prior RT or surgery) treated with RT from 2008 to 2013 were retrospectively reviewed. Spinal Instability Neoplastic Score (SINS) [...]

Menée à partir des données des registres américains des cancers portant sur 460 patientes atteintes d'un adénocarcinome de l'endomètre de stade I, inopérable et traité par radiothérapie, cette étude met en évidence une association entre l'utilisation de la curiethérapie et une amélioration de la survie des patientes

Brachytherapy is associated with improved survival in inoperable stage I endometrial adenocarcinoma: A population-based analysis

Acharya, Sahaja ; Perkins, Stephanie M. ; DeWees, Todd ; Fischer-Valuck, Benjamin ; Mutch, David G. ; Powell, Matthew A. ; Schwarz, Julie K. ; Grigsby, Perry W.

Purpose/Objective : To assess the use of brachytherapy (BT) with or without external beam radiation (EBRT) in inoperable stage I endometrial adenocarcinoma in the United States and to determine the effect of BT on overall survival (OS) and cause specific survival (CSS). Material/Methods : Data between 1998 and 2011 from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database were analyzed. Coarsened exact matching (CEM) was used to adjust for differences in [...]

Menée à partir de données portant sur 30 patients atteints cancer de la glotte de stade T1 (durée médiane de suivi : 30 mois), cette étude évalue l'efficacité, du point de vue du taux de contrôle local à 2 ans, et la faisabilité de l'irradiation d'une seule corde vocale par radiothérapie hypofractionnée avec modulation d'intensité et guidage à l'aide de l'imagerie

Single vocal cord irradiation (SVCI): image-guided intensity-modulated hypofractionated radiotherapy for T1a glottic cancer: early clinical results

Al-Mamgani, Abrahim ; Kwa, Stefan L. S. ; Tans, Lisa ; Moring, Michael ; Fransen, Dennie ; Mehilal, Robert ; Verduijn, Gerda M. ; Baatenburg de Jong, Rob J. ; Heijmen, Ben J. M. ; Levendag, Peter C.

Purpose/objectives : This retrospective analysis of prospectively collected data reports on feasibility, outcome, toxicity, and voice-handicap index (VHI) of patients with T1a glottic cancer treated by a novel IMRT technique developed at our institution to treat only the involved vocal cord; the single vocal cord irradiation (SVCI). Methods and Materials : Thirty patients with T1a glottic cancer were treated by means of SVCI. Dose prescription was set to 16*3.63 Gy (TD 58.08 Gy). The clinical [...]

Cet article passe en revue les travaux récents sur le développement de thérapies ciblées pour le traitement des patients atteints d'un carcinome hépatocellulaire

Advances in targeted therapies for hepatocellular carcinoma in the genomic era

Llovet, Josep M. ; Villanueva, Augusto ; Lachenmayer, Anja ; Finn, Richard S.

Mortality owing to liver cancer has increased in the past 20 years, and the latest estimates indicate that the global health burden of this disease will continue to grow. Most patients with hepatocellular carcinoma (HCC) are still diagnosed at intermediate or advanced disease stages, where curative approaches are often not feasible. Among the treatment options available, the molecular targeted agent sorafenib is able to significantly increase overall survival in these patients. Thereafter, up [...]

Menée in vitro et à l'aide d'un modèle murin de lymphome disséminé, cette étude évalue l'activité antitumorale d'une stratégie basée sur des lymphocytes T emportant à leur surface des nanoparticules chargées en agent cytotoxique (SN-38)

Active targeting of chemotherapy to disseminated tumors using nanoparticle-carrying T cells

Huang, Bonnie ; Abraham, Wuhbet D. ; Zheng, Yiran ; Bustamante López, Sandra C. ; Luo, Samantha S. ; Irvine, Darrell J.

Tumor cells disseminate into compartments that are poorly accessible from circulation, which necessitates high doses of systemic chemotherapy. However, the effectiveness of many drugs, such as the potent topoisomerase I poison SN-38, is hampered by poor pharmacokinetics. To deliver SN-38 to lymphoma tumors in vivo, we took advantage of the fact that healthy lymphocytes can be programmed to phenocopy the biodistribution of the tumor cells. In a murine model of disseminated lymphoma, we expanded [...]

Menée à l'aide de modèles murins, cette étude met en évidence des mécanismes permettant de rendre compte de l'inefficacité des traitements anti-angiogéniques administrés en adjuvant

Investigation of the Lack of Angiogenesis in the Formation of Lymph Node Metastases

Jeong, Han-Sin ; Jones, Dennis ; Liao, Shan ; Wattson, Daniel A. ; Cui, Cheryl H. ; Duda, Dan G. ; Willett, Christopher G. ; Jain, Rakesh K. ; Padera, Timothy P.

Background: To date, antiangiogenic therapy has failed to improve overall survival in cancer patients when used in the adjuvant setting (local-regional disease with no detectable systemic metastasis). The presence of lymph node metastases worsens prognosis, however their reliance on angiogenesis for growth has not been reported. Methods: Here, we introduce a novel chronic lymph node window (CLNW) model to facilitate new discoveries in the growth and spread of lymph node metastases. We use the [...]

Cet article passe en revue les travaux récents sur les immunothérapies anticancéreuses à base d'inhibiteurs de points de contrôle immunitaire

The Evolving Role of Immune Checkpoint Inhibitors in Cancer Treatment

Pennock, Gregory K. ; Chow, Laura Q.M.

Traditional treatment modalities for advanced cancer (radiotherapy, chemotherapy, or targeted agents) act directly on tumors to inhibit or destroy them. Along with surgery, these modalities are predominantly palliative, with toxicity and only modest improvements in survival in patients with advanced solid tumors. Accordingly, long-term survival rates for most patients with advanced cancer remain low, thus there is a need for cancer treatments with favorable benefit and toxicity profiles that [...]

Menée in vitro et in vivo, cette étude suggère l'intérêt des inhibiteurs de PARP pour le traitement des patients atteints d'une tumeur présentant un gène ARID1A muté

ARID1A Deficiency Impairs the DNA Damage Checkpoint and Sensitizes Cells to PARP Inhibitors

Shen, Jianfeng ; Peng, Yang ; Wei, Leizhen ; Zhang, Wei ; Yang, Lin ; Lan, Li ; Kapoor, Prabodh ; Ju, Zhenlin ; Mo, Qianxing ; Shih, Ie-Ming ; Uray, Ivan P. ; Wu, Xiangwei ; Brown, Powel H. ; Shen, Xuetong ; Mills, Gordon B. ; Peng, Guang

ARID1A, SWI/SNF chromatin remodeling complex subunit, is a recently identified tumor suppressor that is mutated in a broad spectrum of human cancers. Thus, it is of fundamental clinical importance to understand its molecular functions and determine whether ARID1A deficiency can be exploited therapeutically. In this article, we report a key function of ARID1A in regulating the DNA damage checkpoint. ARID1A is recruited to DNA double-strand breaks (DSB) via its interaction with the upstream DNA [...]

Menée in vitro et in vivo, cette étude met en évidence l'intérêt d'une stratégie basée sur l'inhibition conjointe des signalisations Hedgehog et FLT3 pour le traitement des patients atteints d'une leucémie myéloïde aiguë présentant des mutations de duplication en tandem interne du gène FLT3

Integration of Hedgehog and mutant FLT3 signaling in myeloid leukemia

Lim, Yiting ; Gondek, Lukasz ; Li, Li ; Wang, Qiuju ; Ma, Haley ; Chang, Emily ; Huso, David L. ; Foerster, Sarah ; Marchionni, Luigi ; McGovern, Karen ; Watkins, David Neil ; Peacock, Craig D. ; Levis, Mark ; Smith, Bruce Douglas ; Merchant, Akil A. ; Small, Donald ; Matsui, William

FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutations resulting in constitutive kinase activity are common in acute myeloid leukemia (AML) and carry a poor prognosis. Several agents targeting FLT3 have been developed, but their limited clinical activity suggests that the inhibition of other factors contributing to the malignant phenotype is required. We examined gene expression data sets as well as primary specimens and found that the expression of GLI2, a major effector [...]

Menée in vitro et in vivo, cette étude suggère l'intérêt d'une stratégie basée sur l'inhibition de DUSP6 pour le traitement de patients atteints d'une leucémie lymphoblastique aiguë

Erk Negative Feedback Control Enables Pre-B Cell Transformation and Represents a Therapeutic Target in Acute Lymphoblastic Leukemia

Shojaee, Seyedmehdi ; Caeser, Rebecca ; Buchner, Maike ; Park, Eugene ; Swaminathan, Srividya ; Hurtz, Christian ; Geng, Huimin ; Chan, Lai N ; Klemm, Lars ; Hofmann, Wolf-Karsten ; Qiu, Yi Hua ; Zhang, Nianxiang ; Coombes, Kevin R ; Paietta, Elisabeth ; Molkentin, Jeffery ; Koeffler, H.  Phillip ; Willman, Cheryl L ; Hunger, Stephen P ; Melnick, Ari ; Kornblau, Steven M ; Müschen, Markus

Studying mechanisms of malignant transformation of human pre-B cells, we found that acute activation of oncogenes induced immediate cell death in the vast majority of cells. Few surviving pre-B cell clones had acquired permissiveness to oncogenic signaling by strong activation of negative feedback regulation of Erk signaling. Studying negative feedback regulation of Erk in genetic experiments at three different levels, we found that Spry2, Dusp6, and Etv5 were essential for oncogenic [...]

Menée à l'aide de modèles murins, cette étude suggère l'intérêt d'une stratégie basée sur l'inhibition de LOX pour le traitement des patients atteints d'un adénocarcinome canalaire pancréatique résécable

Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy

Miller, Bryan W. ; Morton, Jennifer P. ; Pinese, Mark ; Saturno, Grazia ; Jamieson, Nigel B. ; McGhee, Ewan ; Timpson, Paul ; Leach, Joshua ; McGarry, Lynn ; Shanks, Emma ; Bailey, Peter ; Chang, David ; Oien, Karin ; Karim, Saadia ; Au, Amy ; Steele, Colin ; Carter, Christopher Ross ; McKay, Colin ; Anderson, Kurt ; Evans, Thomas R. Jeffry ; Marais, Richard ; Springer, Caroline ; Biankin, Andrew ; Erler, Janine T. ; Sansom, Owen J.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related mortality. Despite significant advances made in the treatment of other cancers, current chemotherapies offer little survival benefit in this disease. Pancreaticoduodenectomy offers patients the possibility of a cure, but most will die of recurrent or metastatic disease. Hence, preventing metastatic disease in these patients would be of significant benefit. Using principal component analysis (PCA), we [...]

Menée in vivo, cette étude évalue l'intérêt de nanoparticules lipidiques embarquant de petits ARNs interférents, ciblés sur la protéine PHB1, pour le traitement des patients atteints d'un cancer du poumon non à petites cellules

Long-circulating siRNA nanoparticles for validating Prohibitin1-targeted non-small cell lung cancer treatment

Zhu, Xi ; Xu, Yingjie ; Solis, Luisa M. ; Tao, Wei ; Wang, Liangzhe ; Behrens, Carmen ; Xu, Xiaoyang ; Zhao, Lili ; Liu, Danny ; Wu, Jun ; Zhang, Ning ; Wistuba, Ignacio I. ; Farokhzad, Omid C. ; Zetter, Bruce R. ; Shi, Jinjun

RNA interference (RNAi) represents a promising strategy for identification and validation of putative therapeutic targets and for treatment of a myriad of important human diseases including cancer. However, the effective systemic in vivo delivery of small interfering RNA (siRNA) to tumors remains a formidable challenge. Using a robust self-assembly strategy, we develop a unique nanoparticle (NP) platform composed of a solid polymer/cationic lipid hybrid core and a lipid-poly(ethylene glycol) [...]

Menée sur des lignées cellulaires de neuroblastome, cette étude met en évidence des mécanismes par lesquels une transition épithélio-mésenchymateuse accompagne le développement d'une résistance au cisplatine

The development of cisplatin resistance in neuroblastoma is accompanied by epithelial to mesenchymal transition in vitro

Piskareva, Olga ; Harvey, Harry ; Nolan, John ; Conlon, Ross ; Alcock, Leah ; Buckley, Patrick ; Dowling, Paul ; O'Sullivan, Finbarr ; Bray, Isabella ; Stallings, Raymond L.

Abstract Neuroblastoma is a challenging childhood malignancy, with a very high percentage of patients relapsing following acquisition of drug resistance, thereby necessitating the identification of mechanisms of drug resistance as well as new biological targets contributing to the aggressive pathogenicity of the disease. In order to investigate the molecular pathways that are involved with drug resistance in neuroblastoma, we have developed and characterised cisplatin resistant sublines [...]

Cet article passe en revue les travaux récents sur les combinaisons de thérapies ciblées pour le traitement des patients atteints d'un lymphome à cellules du manteau

Refining the Mantle Cell Lymphoma Paradigm: Impact of Novel Therapies on Current Practice

Avivi, Irit ; Goy, Andre

Although mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin lymphoma, proactive research efforts fueled by challenges in the management of MCL have led to an increase in median overall survival (OS) of 2.5 years in the mid 1990s to beyond 5 years nowadays. This improvement is due mostly to the use of dose-intensive strategies, particularly cytarabine-containing regimens (with or without high-dose therapy [HDT] followed by autologous stem cell transplantation [ASCT] consolidation), [...]

Mené sur 37 patients atteints d'un lymphome non hodgkinien T périphérique réfractaire ou récidivant, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité de l'alisertib

Phase II Intergroup Trial of Alisertib in Relapsed and Refractory Peripheral T-Cell Lymphoma and Transformed Mycosis Fungoides: SWOG 1108

Barr, Paul M. ; Li, Hongli ; Spier, Catherine ; Mahadevan, Daruka ; LeBlanc, Michael ; Ul Haq, Mansoor ; Huber, Bryan D. ; Flowers, Christopher R. ; Wagner-Johnston, Nina D. ; Horwitz, Steven M. ; Fisher, Richard I. ; Cheson, Bruce D. ; Smith, Sonali M. ; Kahl, Brad S. ; Bartlett, Nancy L. ; Friedberg, Jonathan W.

Purpose : Aurora A kinase (AAK) is upregulated in highly proliferative lymphomas, suggesting its potential as a therapeutic target. Alisertib is a novel oral AAK inhibitor without adverse safety signals in early-phase studies that demonstrated preliminary activity in T-cell lymphoma. This phase II study was conducted to further investigate the efficacy of alisertib in relapsed or refractory peripheral T-cell non-Hodgkin lymphoma (PTCL). Patients and Methods : Eligible patients with [...]

Cet article passe en revue les travaux récents sur les événements indésirables de nature immunitaire associés à l'ipilimumab dans le traitement des patients atteints d'un mélanome métastatique

Immune-mediated Adverse Effects of Anti-CTLA-4 Antibody Therapy in Metastatic Melanoma

Quirk, Shannon K. ; Shure, Anna K. ; Agrawal, Devendra K.

Ipilimumab, an antibody that blocks cytotoxic T lymphocyte-associated antigen-4 (CTLA-4; CD152), was approved by the Food and Drug Administration (FDA) in 2011 for the treatment of unresectable stage III or IV malignant melanoma. Although the addition of this particular immunotherapy has broadened treatment options, immune-related adverse events (irAEs) are associated with ipilimumab therapy, including dermatologic effects, colitis and diarrhea, endocrine effects, hepatotoxicity, ocular [...]

Mené sur 331 patients atteints d'un carcinome rénal à cellules claires de stade métastatique, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de 4 traitements (bévacizumab seul, bévacizumab + temsirolimus, bévacizumab + sorafénib, sorafénib + temsirolimus)

BEST: A Randomized Phase II Study of Vascular Endothelial Growth Factor, RAF Kinase, and Mammalian Target of Rapamycin Combination Targeted Therapy With Bevacizumab, Sorafenib, and Temsirolimus in Advanced Renal Cell Carcinoma—A Trial of the ECOG–ACRIN Cancer Research Group (E2804)

Flaherty, Keith T. ; Manola, Judith B. ; Pins, Michael ; McDermott, David F. ; Atkins, Michael B. ; Dutcher, Janice J. ; George, Daniel J. ; Margolin, Kim A. ; DiPaola, Robert S.

Purpose : On the basis of evidence that resistance to vascular endothelial growth factor (VEGF) receptor inhibition is caused by hypoxia-driven residual VEGF and other proangiogenic factors, combinations of agents from these classes were hypothesized to improve treatment outcomes relative to single-agent VEGF pathway blockade. Patients and Methods : A total of 361 patients with metastatic clear cell renal cell carcinoma were randomly assigned equally to arm A (bevacizumab monotherapy 10 mg/kg [...]

Cet article passe en revue les travaux récents sur les thérapies ciblées, seules ou en combinaison, pour le traitement des patientes atteintes d'un cancer métastatique du sein ER+/HER2-

Targeted therapies for ER+/HER2- metastatic breast cancer

Mutsuko Yamamoto-Ibusuki, ; Monica Arnedos, ; Fabrice André

The majority of breast cancers present with estrogen receptor (ER)-positive and human epidermal growth factor receptor (HER2)-negative features and might benefit from endocrine therapy. Although endocrine therapy has notably evolved during the last decades, the invariable appearance of endocrine resistance, either primary or secondary, remains an important issue in this type of tumor. The improvement of our understanding of the cancer genome has identified some promising targets that might be [...]

Mené sur 3 patients atteints d'un glioblastome récidivant, cet essai évalue la faisabilité d'une administration intracrânienne d'un traitement à base de lymphocytes T modifiés pour exprimer un récepteur d'antigène chimérique ciblant IL13Ralpha2

Bioactivity and Safety of IL13Ralpha2-Redirected Chimeric Antigen Receptor CD8+ T cells in Patients with Recurrent Glioblastoma

Brown, Christine E. ; Badie, Behnam ; Barish, Michael E. ; Weng, Lihong ; Ostberg, Julie R ; Chang, Wen-Chung ; Naranjo, Araceli ; Starr, Renate ; Wagner, Jamie ; Wright, Christine ; Zhai, Yubo ; Bading, James ; Ressler, Julie A ; Portnow, Jana ; D'Apuzzo, Massimo ; Forman, Stephen J. ; Jensen, Michael C.

Purpose: A first-in-human pilot safety and feasibility trial evaluating chimeric antigen receptor (CAR) engineered, autologous primary human CD8+ cytolytic T lymphocytes (CTLs) targeting IL13Rα2 for the treatment of recurrent glioblastoma (GBM). Experimental Design: Three patients with recurrent GBM were treated with IL13(E13Y)-zetakine CD8+ CTL targeting IL13Rα2. Patients received up to twelve local infusions at a maximum dose of 108 CAR-engineered T cells via a catheter/reservoir system. [...]

Mené sur 130 patientes atteintes d'un cancer métastatique du corps de l'utérus (âge médian : 66 ans), cet essai multicentrique randomisé de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité du ridaforolimus

Randomized Phase II Trial of Ridaforolimus in Advanced Endometrial Carcinoma

Oza, Amit M. ; Pignata, Sandro ; Poveda, Andres ; McCormack, Mary ; Clamp, Andrew ; Schwartz, Benjamin ; Cheng, Jonathan ; Li, Xiaoyun ; Campbell, Kristy ; Dodion, Pierre ; Haluska, Frank G.

Purpose : The prognosis for women with recurrent and metastatic endometrial cancer is poor, and improved therapies are needed. The mammalian target of rapamycin (mTOR) pathway is an important target, and mTOR inhibitors show clinical activity in endometrial cancer. Patients and Methods : An open-label, multicenter, randomized, phase II trial of oral ridaforolimus compared with progestin or investigator choice chemotherapy (comparator) was undertaken in women with metastatic or recurrent [...]

Mené en France sur 186 patients atteints d'un cancer des voies biliaires de stade avancé (durée médiane de suivi : 26,4 mois), cet essai multicentrique compare l'efficacité, du point de vue de la survie globale et de la survie sans progression, de plusieurs protocoles de chimiothérapie de deuxième ligne

Second-line chemotherapy for advanced biliary tract cancer after failure of the gemcitabine-platinum combination: A large multicenter study by the Association des Gastro-Entérologues Oncologues

Brieau, Bertrand ; Dahan, Laetitia ; De Rycke, Yann ; Boussaha, Tarek ; Vasseur, Philippe ; Tougeron, David ; Lecomte, Thierry ; Coriat, Romain ; Bachet, Jean-Baptiste ; Claudez, Pierre ; Zaanan, Aziz ; Soibinet, Pauline ; Desrame, Jérome ; Thirot-Bidault, Anne ; Trouilloud, Isabelle ; Mary, Florence ; Marthey, Lysiane ; Taieb, Julien ; Cacheux, Wulfran ; Lièvre, Astrid

BACKGROUND Few data are available on second-line chemotherapy (CT2) for advanced biliary tract cancer (ABTC). The aim of this multicenter study was to describe the CT2 regimens used, the response rates, and the outcomes of patients treated with various CT2 regimens. METHODS Patients who received CT2 for ABTC at 17 French institutions after the failure of the gemcitabine-platinum combination were retrospectively studied. Progression-free survival (PFS) and overall survival (OS) were estimated [...]

Mené sur 14 patients atteints d'un cancer du pancréas de stade localement avancé, cet essai de phase I évalue la dose maximale tolérée, l'efficacité, du point de vue de la survie sans progression, et la toxicité du panitumumab dans le cadre d'un traitement combinant une chimiothérapie à base de gemcitabine et une radiothérapie

Phase I clinical trial to determine the feasibility and maximum tolerated dose of panitumumab to standard gemcitabine-based chemoradiation in locally advanced pancreatic cancer

van Zweeden, Annette A ; van der Vliet, Hans J. ; Wilmink, Johanna W ; Meijerink, Martijn R ; Meijer, Otto WM ; Bruynzeel, Anna ME ; van Tienhoven, Geertjan ; Giovannetti, Elisa ; Kazemier, Geert ; Jacobs, Maarten AJM ; Verheul, Henk M.W.

Purpose : Epidermal Growth Factor receptor (EGFR) inhibitors may improve both the therapeutic efficacy of radiotherapy and the radiosensitizing activity of gemcitabine. Based on this rationale and the non-overlapping toxicity profiles of gemcitabine and the monoclonal EGFR antibody panitumumab, we designed a phase I trial to investigate the maximum-tolerated dose (MTD), safety and activity of panitumumab added to gemcitabine-based chemoradiotherapy (CRT) in patients with locally advanced [...]

Mené sur 27 patients atteints d'un cancer du poumon non à petites cellules de stade III et non résécable (durée médiane de suivi : 26,7 mois), cet essai chinois de phase I/II évalue la faisabilité d'ajouter le cetuximab à une chimiothérapie d'induction par vinorelbine-cisplatine suivie d'un traitement combinant de manière concomitante vinorelbine-cisplatine-cetuximab et radiothérapie thoracique

Induction Chemotherapy with Cetuximab, Vinorelbine-Cisplatin followed by Thoracic Radiotherapy and Concurrent Cetuximab, Vinorelbine-Cisplatin in Patients with Unresectable Stage III Non-Small Cell Lung Cancer

Liu, Di ; Zheng, Xiao ; Chen, Jiayan ; Liu, Guan ; Xu, Yaping ; Shen, Yuxin ; Xie, Liyi ; Zhao, Weixin ; Jiang, Guoliang ; Fan, Min

Objectives : The modest benefits from concurrent chemoradiotherapy (CCRT) in patients with stage III non-small cell lung cancer (NSCLC) warrant a more effective treatment regimen. We herein report mature data of a phase I/II study testing the addition of cetuximab to induction vinorelbine/cisplatin (NP) followed by concurrent cetuximab NP and thoracic radiation in patients with unresectable stage III NSCLC. Materials and Methods : Eligible patients were treated with weekly cetuximab (initial [...]

Menée sur des cellules de glioblastome et à l'aide d'un modèle murin, cette étude montre que le dichloroacétate, un inhibiteur de la pyruvate déshydrogénase kinase 1, peut sensibiliser les cellules tumorales aux rayonnements ionisants en agissant sur le métabolisme du glucose

Sensitization of glioblastoma cells to irradiation by modulating the glucose metabolism

Shen, Han ; Hau, Eric ; Joshi, Swapna ; Dilda, Pierre J ; McDonald, Kerrie L

Since radiotherapy (RT) significantly increases median survival in patients with glioblastoma (GBM), the modulation of radiation resistance is of significant interest. High glycolytic states of tumor cells are known to correlate strongly with radioresistance, thus the concept of metabolic targeting needs to be investigated in combination with RT. Metabolically, the elevated glycolysis in GBM cells was observed post-RT together with upregulated hypoxia inducible factor (HIF)-1