Menée in vitro et à l'aide de xénogreffes, cette étude montre que Sym004, une préparation d'anticorps ciblant le récepteur EGFR, peut améliorer la réponse à une radiothérapie des cellules cancéreuses du poumon ou des voies aérodigestives supérieures

Sym004, a novel anti-EGFR antibody mixture augments radiation response in human lung and head and neck cancers

Huang, Shyh-Min ; Peet, Chimera R. ; Saker, Jarob ; Li, Chunrong ; Armstrong, Eric A. ; Kragh, Michael ; Pedersen, Mikkel W. ; Harari, Paul M

Sym004 represents a novel EGFR targeting approach comprised of a mixture of two anti-EGFR antibodies directed against distinct epitopes of EGFR. In contrast to single anti-EGFR antibodies, Sym004 induces rapid and highly efficient degradation of EGFR. In the current study, we examine the capacity of Sym004 to augment radiation response in lung cancer and head and neck (H&N) cancer model systems. We first examined the anti-proliferative effect of Sym004 and confirmed 40~60% growth inhibition by [...]

Menée in vitro et à l'aide de xénogreffes de cancer du sein, cette étude met en évidence un mécanisme par lequel le 3,3′-diindolylméthane protège les cellules saines des rayonnements ionisants

DIM (3,3′-diindolylmethane) confers protection against ionizing radiation by a unique mechanism

Fan, Saijun ; Meng, Qinghui ; Xu, Jiaying ; Jiao, Yang ; Zhao, Lin ; Zhang, Xiaodong ; Sarkar, Fazlul H. ; Brown, Milton L. ; Dritschilo, Anatoly ; Rosen, Eliot M.

DIM (3,3′-diindolylmethane), a small molecule compound, is a proposed cancer preventive agent that can be safely administered to humans in repeated doses. We report that administration of DIM in a multidose schedule protected rodents against lethal doses of total body irradiation up to 13 Gy, whether DIM dosing was initiated before or up to 24 h after radiation. Physiologic submicromolar concentrations of DIM protected cultured cells against radiation by a unique mechanism: DIM caused rapid [...]

Menée sur 113 patients atteints d'un mélanome desmoplastique traité par résection entre 1989 et 2010 (durée médiane de suivi : 43,1 mois), cette étude montre qu'une radiothérapie adjuvante peut améliorer le contrôle local de la maladie

Radiotherapy influences local control in patients with desmoplastic melanoma

Strom, Tobin ; Caudell, Jimmy J. ; Han, Dale ; Zager, Jonathan S. ; Yu, Daohai ; Cruse, C. Wayne ; Marzban, Suroosh S. ; Messina, Jane L. ; Trotti, Andy M. ; Sondak, Vernon K. ; Rao, Nikhil G.

BACKGROUND : Desmoplastic melanoma may have a high risk of local recurrence after wide excision. The authors hypothesized that adjuvant radiotherapy (RT) would improve local control in patients with desmoplastic melanoma, resulting in at least a 10% absolute decrease in local recurrence rate. METHODS : A total of 277 patients from 1989 through 2010 who were treated for nonmetastatic desmoplastic melanoma by surgery with or without adjuvant RT were reviewed. Clinicopathologic and treatment [...]

Menée à partir de données portant sur 130 patients atteints d'un mélanome desmoplastique non métastatique diagnostiqué entre 1985 et 2009 (âge : 21 à 97 ans, durée médiane de suivi : 6,6 ans), cette étude rétrospective évalue, du point de vue des taux de survie spécifique, de survie globale et de récidive locale à 5 et 10 ans, l'intérêt d'une radiothérapie après une intervention chirurgicale

The role of adjuvant radiotherapy in the local management of desmoplastic melanoma

Guadagnolo, B. Ashleigh ; Prieto, Victor ; Weber, Randal ; Ross, Merrick I. ; Zagars, Gunar K.

BACKGROUND : In the current study, the authors sought to evaluate outcomes, specifically with respect to adjuvant radiotherapy (RT), for patients with desmoplastic melanoma. METHODS : The records of 130 consecutive patients who presented between 1985 and 2009 with nonmetastatic desmoplastic melanoma and were treated curatively with either surgery alone (59 patients; 45%) or surgery and postoperative RT (71 patients; 55%) were retrospectively reviewed. Ages ranged from 21 years to 97 years [...]

Mené sur 79 patients atteints d'un cancer du poumon non à petites cellules, cet essai de phase I évalue la toxicité et la dose maximale tolérée d'une radiothérapie hypofractionnée avec escalade de doses

Dose-Limiting Toxicity After Hypofractionated Dose-Escalated Radiotherapy in Non–Small-Cell Lung Cancer

Cannon, Donald M. ; Mehta, Minesh P. ; Adkison, Jarrod B. ; Khuntia, Deepak ; Traynor, Anne M. ; Tomé, Wolfgang A. ; Chappell, Richard J. ; Tolakanahalli, Ranjini ; Mohindra, Pranshu ; Bentzen, Søren M. ; Cannon, George M.

Purpose : Local failure rates after radiation therapy (RT) for locally advanced non–small-cell lung cancer (NSCLC) remain high. Consequently, RT dose intensification strategies continue to be explored, including hypofractionation, which allows for RT acceleration that could potentially improve outcomes. The maximum-tolerated dose (MTD) with dose-escalated hypofractionation has not been adequately defined. Patients and Methods : Seventy-nine patients with NSCLC were enrolled on a prospective [...]

Menée in vitro et in vivo, cette étude évalue l'activité antitumorale d'un composé appelé TAS-115, un inhibiteur de VEGFR et MET

The novel VEGF receptor/MET-targeted kinase inhibitor, TAS-115, has marked in vivo anti-tumor properties and a favorable tolerability profile

Fujita, Hidenori ; Miyadera, Kazutaka ; Kato, Masanori ; Fujioka, Yayoi ; Ochiiwa, Hiroaki ; Huang, Jinhong ; Ito, Kimihiro ; Aoyagi, Yoshimi ; Takenaka, Toru ; Suzuki, Takamasa ; Ito, Satoko ; Hashimoto, Akihiro ; Suefuji, Takashi ; Egami, Kosuke ; Kazuno, Hideki ; Suda, Yoshimitsu ; Nishio, Kazuto ; Yonekura, Kazuhiko

Vascular endothelial growth factor receptor (VEGFR) signaling plays a key role in tumor angiogenesis. Although some VEGFR signal-targeted drugs have been approved for clinical use, their utility is limited by associated toxicities or resistance to such therapy. To overcome these limitations, we developed TAS-115, a novel VEGFR and hepatocyte growth factor receptor (MET) targeted kinase inhibitor with an improved safety profile. TAS-115 inhibited the kinase activity of both VEGFR2 and MET and [...]

Menée in vitro et in vivo, cette étude met en évidence l'intérêt d'une nouvelle stratégie de type « promédicament » appliquée au ciblage du récepteur EGFR

Tumor-Specific Activation of an EGFR-Targeting Probody Enhances Therapeutic Index

Desnoyers, Luc R. ; Vasiljeva, Olga ; Richardson, Jennifer H. ; Yang, Annie ; Menendez, Elizabeth E. M. ; Liang, Tony W. ; Wong, Chihunt ; Bessette, Paul H. ; Kamath, Kathy ; Moore, Stephen J. ; Sagert, Jason G. ; Hostetter, Daniel R. ; Han, Fei ; Gee, Jason ; Flandez, Jeanne ; Markham, Kate ; Nguyen, Margaret ; Krimm, Michael ; Wong, Kenneth R. ; Liu, Shouchun ; Daugherty, Patrick S. ; West, James W. ; Lowman, Henry B.

Target-mediated toxicity constitutes a major limitation for the development of therapeutic antibodies. To redirect the activity of antibodies recognizing widely distributed targets to the site of disease, we have applied a prodrug strategy to create an epidermal growth factor receptor (EGFR)–directed Probody therapeutic—an antibody that remains masked against antigen binding until activated locally by proteases commonly active in the tumor microenvironment. In vitro, the masked Probody showed [...]

Menée à l'aide d'un modèle murin, cette étude met en évidence l'intérêt du crizotinib pour le traitement adjuvant de patients atteints d'un mélanome primitif de l'uvée

Crizotinib, a c-Met Inhibitor, Prevents Metastasis in a Metastatic Uveal Melanoma Model

Surriga, Oliver ; Rajasekhar, Vinagolu K ; Ambrosini, Grazia ; Dogan, Yildirim ; Huang, Ruimin ; Schwartz, Gary K.

Uveal melanoma is the most common primary intraocular malignant tumor in adults and half of the primary tumors will develop fatal metastatic disease to the liver and the lung. Crizotinib, an inhibitor of c-Met, anaplastic lymphoma kinase (ALK) and ROS1, inhibited the phosphorylation of the c-Met receptor but not of ALK or ROS1 in uveal melanoma cells and tumor tissue. Consequently, migration of uveal melanoma cells was suppressed in vitro at a concentration associated with the specific [...]

Menée à l'aide de xénogreffes, cette étude suggère qu'une stratégie basée sur l'inhibition simultanée des récepteurs HER et VEGFR pourrait être utile pour le traitement de certains sous-groupes de tumeurs de l'ovaire

Dual HER/VEGF receptor targeting inhibits in vivo ovarian cancer tumor growth

Becker, Marc A ; Farzan, Thahir ; Harrington, Sean C. ; Krempski, James ; Weroha, S. John ; Hou, Xiaonan ; Kalli, Kimberly R. ; Wong, Tai W. ; Haluska, Paul

Ovarian cancer mortality ranks highest among all gynecological cancers with growth factor pathways playing an integral role in tumorigenesis, metastatic dissemination and therapeutic resistance. The human epidermal growth factor receptor (HER) and vascular endothelial growth factor receptor (VEGFR) are both overexpressed and/or aberrantly activated in subsets of ovarian tumors. While agents targeting either the HER or VEGF pathways alone have been investigated, the impact of these agents have [...]

Menée sur une lignée cellulaire de cancer du poumon non à petites cellules présentant la translocation EML4-ALK, cette étude met en évidence un mécanisme par lequel l'activation du récepteur EGFR induit une résistance au crizotinib

Dual ALK and EGFR inhibition targets a mechanism of acquired resistance to the tyrosine kinase inhibitor crizotinib in ALK rearranged lung cancer

Yamaguchi, Norihiro ; Lucena-Araujo, Antonio R. ; Nakayama, Sohei ; de Figueiredo-Pontes, Lorena L. ; Gonzalez, David A. ; Yasuda, Hiroyuki ; Kobayashi, Susumu ; Costa, Daniel B.

Introduction The multitargeted tyrosine kinase inhibitor (TKI) crizotinib is active against ALK translocated non-small-cell lung cancer (NSCLC); however acquired resistance invariably develops over time. ALK mutations have previously been implicated in only a third of resistant tumors. We sought to evaluate alternative mechanisms of resistance and preclinical strategies to overcome these in a cell line driven by EML4-ALK. Methods We selected the NSCLC cell line NCI-H3122 (H3122: EML4-ALK [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes impliquant la voie de signalisation IGFBP2/FAK dans la résistance au dasatinib pour le traitement d'un cancer du poumon non à petites cellules

IGFBP2/FAK pathway is causally associated with dasatinib resistance in non-small cell lung cancer cells

Lu, Haibo ; Wang, Li ; Gao, Wen ; Meng, Jieru ; Dai, Bingbing ; Wu, Shuhong ; Minna, John D. ; Roth, Jack A. ; Hofstetter, Wayne L ; Swisher, Stephen G ; Fang, Bingliang

IGFBP2 expression is increased in various types of cancers, including in a subset of lung cancer patients. Because IGFBP2 is involved in signal transduction of some critical cancer related pathways, we analyzed the association between IGFBP2 and response to pathway-targeted agents in seven human non-small cell lung cancer (NSCLC) cell lines. Western blot analysis and enzyme-linked immunosorbent assay (ELISA) showed that four of the seven NSCLC cell lines analyzed expressed high levels of [...]

Cet article passe en revue les travaux récents sur les mécanismes de résistance aux inhibiteurs de tyrosine kinase dans les traitements de patients atteints d'un carcinome rénal à cellules claires

Resistance to tyrosine kinase inhibitors in clear cell renal cell carcinoma: From the patient’s bed to molecular mechanisms

Buczek, Magdalena ; Escudier, Bernard ; Bartnik, Ewa ; Szczylik, Cezary ; Czarnecka, Anna

The introduction of anti-angiogenic drugs especially Tyrosine Kinase Inhibitors (TKIs) was a breakthrough in the treatment of renal cell carcinoma (RCC). Although TKIs have significantly improved outcome in patients with metastatic disease, the majority still develop resistance over time. Because different combinations and sequences of TKIs are tested in clinical trials, resistance patterns and mechanisms underlying this phenomenon should be thoroughly investigated. From a clinical point of [...]

Cet article passe en revue les perspectives offertes par les nanotechnologies pour développer des traitements d'un cancer du cerveau

Nanotherapeutic approaches for brain cancer management

del Burgo, Laura Saenz ; Hernández, Rosa María ; Orive, Gorka ; Pedraz, Jose Luis

Around the world, cancer remains one of the most important causes of morbidity and mortality. Worldwide, approximately 238,000 new cases of brain and other central nervous system tumors are diagnosed every year. Nanotherapeutic approaches hold tremendous potential for diagnosis and treatment of brain cancer, including the ability to target complex molecular cargoes to the tumor sites and the capacity of crossing the blood-brain-barrier and accessing to the brain after systemic administration. A [...]

Cet article passe en revue les travaux récents sur la durée optimale de traitement par inhibiteur de tyrosine kinase tel que l'imatinib chez les patients ayant subi une résection chirurgicale d'une tumeur stromale gastrointestinale

Optimizing Tyrosine Kinase Inhibitor Therapy in Gastrointestinal Stromal Tumors: Exploring the Benefits of Continuous Kinase Suppression

Le Cesne, Axel ; Blay, Jean-Yves ; Reichardt, Peter ; Joensuu, Heikki

Background. The oral tyrosine kinase inhibitor (TKI) imatinib has revolutionized the treatment of gastrointestinal stromal tumors (GISTs), most of which harbor oncogenic mutation in genes that encode the receptor tyrosine kinases KIT or PDGFA. Imatinib is the standard of care for patients with advanced GIST and for patients with primary GIST at significant risk of recurrence after surgery. Design. This review discusses data supporting continuous kinase suppression with imatinib and key issues, [...]

Mené sur 472 patients atteints d'une leucémie myéloïde aiguë récemment diagnostiquée (âge compris entre 61 et 75 ans), cet essai de phase III évalue l'efficacité, du point de vue de la survie globale, et la toxicité d'un traitement séquentiel à l'aide de gemtuzumab ozogamicine

Sequential Combination of Gemtuzumab Ozogamicin and Standard Chemotherapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia: Results of a Randomized Phase III Trial by the EORTC and GIMEMA Consortium (AML-17)

Amadori, Sergio ; Suciu, Stefan ; Stasi, Roberto ; Salih, Helmut R. ; Selleslag, Dominik ; Muus, Petra ; De Fabritiis, Paolo ; Venditti, Adriano ; Ho, Anthony D. ; Lübbert, Michael ; Thomas, Xavier ; Latagliata, Roberto ; Halkes, Constantijn J.M. ; Falzetti, Franca ; Magro, Domenico ; Guimaraes, José E. ; Berneman, Zwi ; Specchia, Giorgina ; Karrasch, Matthias ; Fazi, Paola ; Vignetti, Marco ; Willemze, Roel ; de Witte, Theo ; Marie, Jean-Pierre

Purpose This randomized trial evaluated the efficacy and toxicity of sequential gemtuzumab ozogamicin (GO) and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia (AML). Patients and Methods Patients (n = 472) age 61 to 75 years were randomly assigned to induction chemotherapy with mitoxantrone, cytarabine, and etoposide preceded, or not, by a course of GO (6 mg/m2 on days 1 and 15). In remission, patients received two consolidation courses with or without GO (3 [...]

Mené sur 44 patients atteints d'un lymphome non hodgkinien récidivant et/ou réfractaire, cet essai français de phase I évalue la doxe maximale recommandée d'un composé appelé SAR3419, un conjugué anticorps-médicament ciblé sur CD19

A Phase I Study of SAR3419, an Anti-CD19 Antibody Maytansinoid Conjuguate, Administered One Weekly In Patients WIth Relapsed/refractory B-Cell Non Hodgkin's Lymphoma

Ribrag, Vincent ; Dupuis, Jehan ; Tilly, Herve ; Morschhauser, Franck ; Laine, Fabrice ; Haioun, Corinne ; Copie, Christiane ; Varga, Andrea ; Lambert, John M ; Ziti-Ljajic, Samira ; Caron, Anne ; Payrard, Sandrine ; Coiffier, Bertrand

Purpose To determine recommended dose (RD), dose-limiting toxicity, safety profile, pharmacokinetics, preliminary antitumor activity and exploratory pharmacodynamic of SAR3419, an antibody-drug conjugate targeting CD19, administered alone by intravenous (IV) infusion weekly (qw), in a dose-escalation phase I study in patients with Refractory/Relapsed (R/R) non Hodgkin's lymphoma (NHL). Experimental design Patients with R/R CD19+ B-NHL were treated with escalating doses of SAR3419 repeated qw [...]

Mené sur 149 patientes atteintes d'un cancer de l'ovaire résistant aux sels de platine, cet essai de phase II évalue, du point de vue de la survie sans progression, l'efficacité de l'ajout de vintafolide à un traitement par doxorubicine liposomale pégylée

PRECEDENT: A Randomized Phase II Trial Comparing Vintafolide (EC145) and Pegylated Liposomal Doxorubicin (PLD) in Combination Versus PLD Alone in Patients With Platinum-Resistant Ovarian Cancer

Naumann, R. Wendel ; Coleman, Robert L. ; Burger, Robert A. ; Sausville, Edward A. ; Kutarska, Elzbieta ; Ghamande, Sharad A. ; Gabrail, Nashat Y. ; DePasquale, Stephen E. ; Nowara, Elzbieta ; Gilbert, Lucy ; Gersh, Robert H. ; Teneriello, Michael G. ; Harb, Wael A. ; Konstantinopoulos, Panagiotis A. ; Penson, Richard T. ; Symanowski, James T. ; Lovejoy, Chandra D. ; Leamon, Christopher P. ; Morgenstern, David E. ; Messmann, Richard A.

Purpose Vintafolide (EC145) is a folic acid–desacetylvinblastine conjugate that binds to the folate receptor (FR), which is expressed on the majority of epithelial ovarian cancers. This randomized phase II trial evaluated vintafolide combined with pegylated liposomal doxorubicin (PLD) compared with PLD alone. The utility of an FR-targeted imaging agent, 99mTc-etarfolatide (EC20), in selecting patients likely to benefit from vintafolide was also examined. Patients and Methods Women with [...]

Cet article passe en revue les travaux récents sur le trastuzumab emtasine pour le traitement des patientes atteintes d'un cancer métastatique du sein HER2+

Trastuzumab emtansine: a novel antibody-drug conjugate for HER2-positive breast cancer

Krop, Ian ; Winer, Eric P

Trastuzumab emtansine (T-DM1) is a novel HER2-directed antibody-drug conjugate. T-DM1 consists of the potent anti-microtubule agent DM1, linked via a non-cleavable linker to the HER2-specific monoclonal antibody trastuzumab. Preclinical studies demonstrate that T-DM1 has dual mechanisms of action: selective delivery of DM1 to the HER2-positive tumor cell combined with trastuzumab's activation of antibody-dependent cellular cytotoxicity and inhibition of HER2 mediated signal transduction. In [...]

A partir de données issues du système d'assurance maladie Medicare et du registre texan des cancers entre 2005 et 2009 (9 355 patientes âgées de plus de 66 ans et atteintes d'un cancer du sein), cette étude évalue le taux d'insuffisance cardiaque congestive liée à un traitement par trastuzumab et identifie les facteurs de risques associés

Trastuzumab-Related Cardiotoxicity Among Older Patients With Breast Cancer

Chavez-MacGregor, Mariana ; Zhang, Ning ; Buchholz, Thomas A. ; Zhang, Yufeng ; Niu, Jiangong ; Elting, Linda ; Smith, Benjamin D. ; Hortobagyi, Gabriel N. ; Giordano, Sharon H.

Purpose The use of trastuzumab in the adjuvant setting improves outcomes but is associated with cardiotoxicity manifested as congestive heart failure (CHF). The rates and risk factors associated with trastuzumab-related CHF among older patients are unknown. Patients and Methods Breast cancer patients at least 66 years old with full Medicare coverage, diagnosed with stage I-III breast cancer between 2005 and 2009, and treated with chemotherapy were identified in the SEER-Medicare and in the [...]

Menée sur une cohorte de 518 patients atteints d'un adénocarcinome de l'œsophage traité entre 2000 et 2010 (âge : 23 à 79 ans ; durée médiane de suivi : 29,3 mois), cette étude évalue le taux d'échec locorégional après une chimioradiothérapie pré-opératoire puis l'intérêt d'un traitement de sauvetage pour améliorer la survie

Locoregional Failure Rate After Preoperative Chemoradiation of Esophageal Adenocarcinoma and the Outcomes of Salvage Strategies

Sudo, Kazuki ; Taketa, Takashi ; Correa, Arlene M. ; Campagna, Maria-Claudia ; Wadhwa, Roopma ; Blum, Mariela A. ; Komaki, Ritsuko ; Lee, Jeffrey H. ; Bhutani, Manoop S. ; Weston, Brian ; Skinner, Heath D. ; Maru, Dipen M. ; Rice, David C. ; Swisher, Stephen G. ; Hofstetter, Wayne L. ; Ajani, Jaffer A.

Purpose : The primary purpose of surveillance of patients with esophageal adenocarcinoma (EAC) and/or esophagogastric junction adenocarcinoma after local therapy (eg, chemoradiotherapy followed by surgery or trimodality therapy [TMT]) is to implement a potentially beneficial salvage therapy to overcome possible morbidity/mortality caused by locoregional failure (LRF). However, the benefits of surveillance are not well understood. We report on LRFs and salvage strategies in a large cohort. [...]

Menée sur 164 patients atteints d'un cancer colorectal et inclus dans un essai de phase II évaluant une chimiothérapie néoadjuvante de type CAPOX et une chimioradiothérapie avec ou sans cétuximab (durée médiane de suivi : 58,6 mois), cette étude évalue la prévalence de l'expression tumorale de HER2 et analyse son impact sur la réponse complète au traitement et la survie globale des patients

HER2 in high-risk rectal cancer patients treated in EXPERT-C, a randomized phase II trial of neoadjuvant capecitabine and oxaliplatin (CAPOX) and chemoradiotherapy (CRT) with or without cetuximab

Sclafani, F. ; Roy, A. ; Cunningham, D. ; Wotherspoon, A. ; Peckitt, C. ; Gonzalez de Castro, D. ; Tabernero, J. ; Glimelius, B. ; Cervantes, A. ; Eltahir, Z. ; Oates, J. ; Chau, I.

Background : HER2 is an established therapeutic target in breast and gastric cancers. The role of HER2 in rectal cancer is unclear, as conflicting data on the prevalence of HER2 expression in this disease have been reported. We evaluated the prevalence of HER2 and its impact on the outcome of high-risk rectal cancer patients treated with neoadjuvant CAPOX and CRT±cetuximab in the EXPERT-C trial. Patients and methods : Eligible patients with available tumour tissue for HER2 analysis were [...]

Mené sur 18 patients présentant un sarcome des tissus mous des extrémités et devant subir une chirurgie de sauvetage du membre atteint, cet essai de phase I détermine la dose maximale tolérée de sorafenib en combinaison avec une chimioradiothérapie pré-opératoire, puis évalue la réponse au traitement par IRM dynamique quantitative de contraste

Phase I Trial of Preoperative Chemoradiation Plus Sorafenib for High Risk Extremity Soft Tissue Sarcomas with Dynamic Contrast-Enhanced MRI Correlates

Meyer, Janelle M. ; Perlewitz, Kelly S. ; Hayden, James B. ; Doung, Yee-Cheen ; Hung, Arthur Y. ; Vetto, John T ; Pommier, Rodney F. ; Mansoor, Atiya ; Beckett, Brooke R. ; Tudorica, Alina ; Mori, Motomi ; Holtorf, Megan L. ; Afzal, Aneela ; Woodward, William ; Rodler, Eve T. ; Jones, Robin L ; Huang, Wei ; Ryan, Christopher W

Purpose : We performed a phase I trial of the addition of sorafenib to a chemoradiotherapy regimen in patients with high-risk (intermediate/high grade, >5 cm) extremity soft tissue sarcoma (STS) undergoing limb salvage surgery. We conducted a correlative study of quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess response to treatment. Experimental Design : Patients were treated at increasing dose levels of sorafenib (200 mg daily, 400 mg daily, 400 mg BID) [...]

Menée sur 345 patients atteints d'un glioblastome, cette étude prospective multicentrique montre qu'une résection complète de la tumeur dans le cadre d'un traitement comportant une chimioradiothérapie prolonge la survie des patients

Gross total but not incomplete resection of glioblastoma prolongs survival in the era of radiochemotherapy

Kreth, F. -W. ; Thon, N. ; Simon, M. ; Westphal, M. ; Schackert, G. ; Nikkhah, G. ; Hentschel, B. ; Reifenberger, G. ; Pietsch, T. ; Weller, M. ; Tonn, J. -C. ; for the German Glioma Network

Background : This prospective multicenter study assessed the prognostic influence of the extent of resection when compared with biopsy only in a contemporary patient population with newly diagnosed glioblastoma. Patients and methods : Histology, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, and clinical data were centrally analyzed. Survival analyses were carried out with the Kaplan–Meier method. Prognostic factors were assessed with proportional hazard models. [...]

A partir d'une revue systématique de la littérature publiée depuis 2006 sur des essais cliniques de phase I (611 essais identifiés), cette étude analyse l'évolution du recours à des cohortes d'extension dans ces essais

Evolution of Clinical Trial Design in Early Drug Development: Systematic Review of Expansion Cohort Use in Single-Agent Phase I Cancer Trials

Manji, Arif ; Brana, Irene ; Amir, Eitan ; Tomlinson, George ; Tannock, Ian F. ; Bedard, Philippe L. ; Oza, Amit ; Siu, Lillian L. ; Abdul Razak, Albiruni R.

Purpose To evaluate the use and objectives of expansion cohorts in phase I cancer trials and to explore trial characteristics associated with their use. Methods We performed a systematic review of MEDLINE and EMBASE, limiting studies to single-agent phase I trials recruiting adults and published after 2006. Eligibility assessment and data extraction were performed by two reviewers. Data were assessed descriptively, and associations were tested by univariable and multivariable logistic [...]