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Accueil Nota Bene Cancer V2 Numéro 132 du 17 Avril 2012 Traitements

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Nota Bene Cancer Numéro 132 du 17 Avril 2012 RSS

Traitements

Traitements localisés : découverte et développement

Menée en France sur 233 patientes atteintes d'un cancer du sein traité entre 2004 et 2008, cette étude prospective multicentrique non randomisée compare la faisabilité et la reproductibilité de trois systèmes de radiothérapie conformationnelle avec asservissement respiratoire

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    Menée en France sur 233 patientes atteintes d'un cancer du sein traité entre 2004 et 2008, cette étude prospective multicentrique non randomisée compare la faisabilité et la reproductibilité de trois systèmes de radiothérapie conformationnelle avec asservissement respiratoire

    “Contribution of Respiratory Gating Techniques for Optimization of Breast Cancer Radiotherapy”

    • Giraud, Philippe;Djadi-Prat, Juliette;Morelle, Magalie;Pourel, Nicolas;Durdux, Catherine;Carrie, Christian;Daveau, Caroline;Carrère, Marie-Odile;, the STIC study centers

    A comparative, nonrandomized, multicenter, and prospective analysis were performed between April 2004 and June 2008 in 20 French centers in order to compare clinical aspects of respiratory-gated conformal radiotherapy (RGRT) during breast cancer irradiation versus conventional conformal radiotherapy. The final results based on 233 evaluable patients at 48 months confirm the feasibility and good reproducibility of the RGRT systems. The main results demonstrated a marked reduction of dosimetric parameters predictive of lungs and cardiac toxicities in the RGRT group; especially the dose delivered to the heart during irradiation of the left breast; mostly observed with deep inspiration breath-hold techniques.


Mots clés : Sein; Traitements (Traitements localisés : découverte et développement)

Menée sur 42 hommes âgés de 45 à 80 ans et atteints d'un cancer localisé unifocal ou multifocal de la prostate, cette étude prospective évalue les effets secondaires d'un traitement par ultrasons focalisés de haute intensité

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    Menée sur 42 hommes âgés de 45 à 80 ans et atteints d'un cancer localisé unifocal ou multifocal de la prostate, cette étude prospective évalue les effets secondaires d'un traitement par ultrasons focalisés de haute intensité

    “Focal therapy for localised unifocal and multifocal prostate cancer: a prospective development study”

    • Ahmed, Hashim U.;Hindley, Richard G.;Dickinson, Louise;Freeman, Alex;Kirkham, Alex P.;Sahu, Mahua;Scott, Rebecca;Allen, Clare;Van der Meulen, Jan;Emberton, Mark

    Radical whole-gland therapy can lead to significant genitourinary and rectal side-effects for men with localised prostate cancer. We report on whether selective focal ablation of unifocal and multifocal cancer lesions can reduce this treatment burden. Men aged 45?80 years were eligible for this prospective development study if they had low-risk to high-risk localised prostate cancer (prostate specific antigen [PSA] ?15 ng/mL, Gleason score ?4?+?3, stage ?T2), with no previous androgen deprivation or treatment for prostate cancer, and who could safely undergo multiparametric MRI and have a general anaesthetic. Patients received focal therapy using high-intensity focused ultrasound, delivered to all known cancer lesions, with a margin of normal tissue, identified on multiparametric MRI, template prostate-mapping biopsies, or both. Primary endpoints were adverse events (serious and otherwise) and urinary symptoms and erectile function assessed using patient questionnaires. Analyses were ...


  • Prostate cancer treatment unblinded
    The Lancet Oncology, sous presse, 2012 (commentaire)
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    Menée sur 42 hommes âgés de 45 à 80 ans et atteints d'un cancer localisé unifocal ou multifocal de la prostate, cette étude prospective évalue les effets secondaires d'un traitement par ultrasons focalisés de haute intensité

    “Prostate cancer treatment unblinded”

    • Tsivian, Matvey ; Abern, Michael R. ; Polascik, Thomas J.


Mots clés : Prostate; Traitements (Traitements localisés : découverte et développement)

Traitements localisés : applications cliniques

Mené sur 100 patientes atteintes d'un cancer du sein de stade 0-IIA, cet essai prospectif définit la position individuelle optimale permettant de traiter par rayonnements ionisants des tumeurs mammaires sans endommager le système cardiovasculaire et les poumons

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    Mené sur 100 patientes atteintes d'un cancer du sein de stade 0-IIA, cet essai prospectif définit la position individuelle optimale permettant de traiter par rayonnements ionisants des tumeurs mammaires sans endommager le système cardiovasculaire et les poumons

    “Prospective Assessment of Optimal Individual Position (Prone Versus Supine) for Breast Radiotherapy: Volumetric and Dosimetric Correlations in 100 Patients”

    • Lymberis, Stella C.;deWyngaert, John Keith;Parhar, Preeti;Chhabra, Arpit M.;Fenton-Kerimian, Maria;Chang, Jengwha;Hochman, Tsivia;Guth, Amber;Roses, Daniel;Goldberg, Judith D.;Formenti, Silvia C.

    Damage to heart and lung from breast radiotherapy is associated with increased cardiovascular mortality and lung cancer development. We conducted a prospective study to evaluate which position is best to spare lung and heart from radiotherapy exposure. One hundred consecutive Stage 0–IIA breast cancer patients consented to participate in a research trial that required two computed tomography simulation scans for planning both supine and prone positions. The optimal position was defined as that which best covered the contoured breast and tumor bed while it minimized critical organ irradiation, as quantified by the in-field heart and lung volume. The trial was designed to plan the first 100 patients in each position to study correlations between in-field volumes of organs at risk and dose. Fifty-three left and 47 right breast cancer patients were consecutively accrued to the trial. In all patients, the prone position was optimal for sparing lung volume compared to the supine setup ...


Mots clés : Sein; Traitements (Traitements localisés : applications cliniques)

Mené sur 100 patientes ménopausées atteintes d'un cancer du sein de stade 1 et ayant reçu un traitement chirurgical conservateur (âge : 53 à 88 ans ; durée médiane de suivi : 64 mois), cet essai prospectif évalue sur 5 ans l'efficacité et la toxicité d'une irradiation partielle accélérée du sein par radiothérapie conformationnelle externe à trois dimensions

  • Prone Accelerated Partial Breast Irradiation After Breast-Conserving Surgery: Five-year Results of 100 Patients
    International journal of radiation oncology, biology, physics, sous presse, 2012 (résumé)
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    Mené sur 100 patientes ménopausées atteintes d'un cancer du sein de stade 1 et ayant reçu un traitement chirurgical conservateur (âge : 53 à 88 ans ; durée médiane de suivi : 64 mois), cet essai prospectif évalue sur 5 ans l'efficacité et la toxicité d'une irradiation partielle accélérée du sein par radiothérapie conformationnelle externe à trois dimensions

    “Prone Accelerated Partial Breast Irradiation After Breast-Conserving Surgery: Five-year Results of 100 Patients”

    • Formenti, Silvia C.;Hsu, Howard;Fenton-Kerimian, Maria;Roses, Daniel;Guth, Amber;Jozsef, Gabor;Goldberg, Judith D.;DeWyngaert, J. Keith

    To report the 5-year results of a prospective trial of three-dimensional conformal external beam radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation in the prone position. Postmenopausal patients with Stage I breast cancer with nonpalpable tumors <2 cm, negative margins and negative nodes, positive hormone receptors, and no extensive intraductal component were eligible. The trial was offered only after eligible patients had refused to undergo standard whole-breast radiotherapy. Patients were simulated and treated on a dedicated table for prone setup. 3D-CRT was delivered at a dose of 30 Gy in five 6-Gy/day fractions over 10 days with port film verification at each treatment. Rates of ipsilateral breast failure, ipsilateral nodal failure, contralateral breast failure, and distant failure were estimated using the cumulative incidence method. Rates of disease-free, overall, and cancer-specific survival were recorded. One hundred patients were enrolled in this ...


Mots clés : Sein; Traitements (Traitements localisés : applications cliniques)

A partir de données d'un registre médical portant sur 356 patients atteints d'un cancer localisé de la prostate de stade T1-T2 et ayant subi une résection complète par ultrasons focalisés de haute intensité entre 1994 et 2009 (durée médiane de suivi : 2,8 ans), cette étude multicentrique évalue le risque de récidive biochimique et le taux de survie sans progression de la maladie à 5 et 7 ans

  • Complete high-intensity focused ultrasound in prostate cancer: outcome from the @-Registry
    Prostate Cancer and Prostatic Diseases, sous presse, 2012 (résumé)
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    A partir de données d'un registre médical portant sur 356 patients atteints d'un cancer localisé de la prostate de stade T1-T2 et ayant subi une résection complète par ultrasons focalisés de haute intensité entre 1994 et 2009 (durée médiane de suivi : 2,8 ans), cette étude multicentrique évalue le risque de récidive biochimique et le taux de survie sans progression de la maladie à 5 et 7 ans

    “Complete high-intensity focused ultrasound in prostate cancer: outcome from the @-Registry”

    • Blana, A.;Robertson, C. N.;Brown, S. C. W.;Chaussy, C.;Crouzet, S.;Gelet, A.;Conti, G. N.;Ganzer, R.;Pasticier, G.;Thuroff, S.;Ward, J. F.

    Background : To analyze data on patients with localized prostate cancer who were treated with complete high-intensity focused ultrasound (HIFU) prospectively captured within a voluntary HIFU user database (@-Registry). Methods : The @-Registry includes data from consecutive patients treated with Ablatherm (EDAP-TMS) HIFU at nine European Centres during the period 1994 and 2009. For this analysis, the data repository was reviewed for information on patients with localized prostate cancer (T1–T2) treated with complete (whole-gland) HIFU on the basis of an anterior-posterior prostate height of less than or equal to24 mm and a treated volume >120% of the prostate volume. Patients were regularly followed with PSA measurement and biopsy. Biochemical failure was defined for this study as PSA nadir +2 ng ml−1 (Phoenix definition). Disease-free survival was based on a biopsy, retreatment and biochemical data. Patients were risk group-stratified using the D'Amico classification ...


Mots clés : Prostate; Traitements (Traitements localisés : applications cliniques)

Traitements systémiques : découverte et développement

Menée in vitro, cette étude évalue les effets d'une petite molécule, une dibenzophénanthridine inhibitrice d'une enzyme du métabolisme, la glutaminase C, sur la prolifération de cellules de cancer du sein

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    Menée in vitro, cette étude évalue les effets d'une petite molécule, une dibenzophénanthridine inhibitrice d'une enzyme du métabolisme, la glutaminase C, sur la prolifération de cellules de cancer du sein

    “Dibenzophenanthridines as inhibitors of phosphate-activated glutaminase C and cancer cell proliferation”

    • Katt, William P.;Ramachandran, Sekar;Erickson, Jon W.;Cerione, Richard A.

    One of the hallmarks of cancer cells is their adaptation to rely upon an altered metabolic scheme that includes changes in the glycolytic pathway, known as the Warburg effect, and elevated glutamine metabolism. As a consequence of these metabolic changes, cancer cells are often described as being addicted to glutamine. Glutaminase, a mitochondrial enzyme, plays a key role in the metabolism of glutamine in cancer cells, and thus its inhibition could significantly impact malignant transformation. The small molecule 968, a dibenzophenanthridine, was recently shown to be an inhibitor of recombinantly expressed glutaminase C, to block the proliferation and anchorage independent colony formation of human cancer cells in culture, and to inhibit tumor formation in mouse xenograft models. Here, we examine the structure-activity relationship and binding mode that leads to 968-based inhibition of glutaminase and cancer cell proliferation, focusing in particular upon a 'hot-spot' ring previously ...


Mots clés : Sein; Traitements (Traitements systémiques : découverte et développement)

Cet article passe en revue les perspectives offertes par le développement de thérapies ciblées pour surmonter la résistance à une hormonothérapie chez des patientes atteintes d'un cancer du sein métastatique

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    Cet article passe en revue les perspectives offertes par le développement de thérapies ciblées pour surmonter la résistance à une hormonothérapie chez des patientes atteintes d'un cancer du sein métastatique

    “Targeted agents to reverse resistance to endocrine therapy in metastatic breast cancer: Where are we now and where are we going?”

    • Fedele, Palma;Calvani, Nicola;Marino, Antonella;Orlando, Laura;Schiavone, Paola;Quaranta, Annamaria;Cinieri, Saverio

    Endocrine therapy is the most important systemic therapy for hormone receptor positive breast cancer; however, some patients with ER+ breast cancer show intrinsic resistance to endocrine therapy, whereas others develop acquired resistance. Preclinical models have shown that endocrine resistance is associated with enhanced expression of membrane growth factor pathways or activation of various intracellular pathways involved in signal transduction and cell survival. Despite encouraging preclinical data, clinical trials investigating the combination of endocrine therapy with trastuzumab or the TKIs gefitinib, erlotinib and lapatinib have yielded varied results. This may be related to some limitations in the studies conducted so far: lack of appropriate patient selection and stratification based on previous endocrine exposure and/or sensitivity; lack of identification of a molecular biomarker; lack of appropriate clinical endpoints in the trial design. More promising results come from ...


Mots clés : Sein; Traitements (Traitements systémiques : découverte et développement)

Menée sur des lignées cellulaires de cancer du sein triplement négatif et à l'aide d'un modèle murin, cette étude met en évidence des mécanismes associés à la résistance à un traitement par inhibiteur de MEK

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    Menée sur des lignées cellulaires de cancer du sein triplement négatif et à l'aide d'un modèle murin, cette étude met en évidence des mécanismes associés à la résistance à un traitement par inhibiteur de MEK

    “Dynamic Reprogramming of the Kinome in Response to Targeted MEK Inhibition in Triple-Negative Breast Cancer”

    • Duncan, James S;Whittle, Martin C;Nakamura, Kazuhiro;Abell, Amy N;Midland, Alicia A;Zawistowski, Jon S;Johnson, Nancy L;Granger, Deborah A;Jordan, Nicole Vincent;Darr, David B;Usary, Jerry;Kuan, Pei-Fen;Smalley, David M;Major, Ben;He, Xiaping;Hoadley, Katherine A;Zhou, Bing;Sharpless, Norman E;Perou, Charles M;Kim, William Y;Gomez, Shawn M;Chen, Xin;Jin, Jian;Frye, Stephen V;Earp, H.  Shelton;Graves, Lee M;Johnson, Gary L

    Kinase inhibitors have limited success in cancer treatment because tumors circumvent their action. Using a quantitative proteomics approach, we assessed kinome activity in response to MEK inhibition in triple-negative breast cancer (TNBC) cells and genetically engineered mice (GEMMs). MEK inhibition caused acute ERK activity loss, resulting in rapid c-Myc degradation that induced expression and activation of several receptor tyrosine kinases (RTKs). RNAi knockdown of ERK or c-Myc mimicked RTK induction by MEK inhibitors, and prevention of proteasomal c-Myc degradation blocked kinome reprogramming. MEK inhibitor-induced RTK stimulation overcame MEK2 inhibition, but not MEK1 inhibition, reactivating ERK and producing drug resistance. The C3Tag GEMM for TNBC similarly induced RTKs in response to MEK inhibition. The inhibitor-induced RTK profile suggested a kinase inhibitor combination therapy that produced GEMM tumor apoptosis and regression where single agents were ineffective. This ...


Mots clés : Sein; Traitements (Traitements systémiques : découverte et développement)

Menée sur des lignées cellulaires de cancer de la prostate, cette étude identifie un nouvel antagoniste du récepteur aux androgènes, MEL-3, et caractérise son activité

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    Menée sur des lignées cellulaires de cancer de la prostate, cette étude identifie un nouvel antagoniste du récepteur aux androgènes, MEL-3, et caractérise son activité

    “Identification and characterization of MEL-3, a novel androgen receptor antagonist that suppresses prostate cancer cell growth”

    • Helsen, Christine;Marchand, Arnaud;Chaltin, Patrick;Munck, Sebastian;Voet, Arnout;Verstuyf, Annemieke;Claessens, Frank

    Anti-androgens are an important component of prostate cancer therapy as the androgen receptor (AR) is the key regulator of prostate cancer growth and survival. Current AR-antagonists, such as Bicalutamide (Bic) and Hydroxyflutamide (HOFl), have a low affinity for the AR and as a result block AR-signaling insufficiently. Moreover, many patients develop a resistance for Bic or HOFl during therapy or show a clinical improvement after withdrawal of the anti-androgen. New and more effective AR-antagonists are needed to ensure follow-up of these patients. We therefore developed a screening system to identify novel AR-antagonists from a collection of compounds. MEL-3 [8-(propan-2-yl)-5,6-dihydro-4H-pyrazino[3,2,1-jk]carbazole] was selected as potent inhibitor of the AR and was further characterized in vitro. On different prostate cancer cell lines MEL-3 displayed an improved therapeutic profile compared to Bic. Not only cell growth was inhibited but also the expression of androgen-regulated ...


Mots clés : Prostate; Traitements (Traitements systémiques : découverte et développement)

Menée in vitro et in vivo, cette étude évalue l'activité antitumorale d'une petite molécule inhibitrice de la voie de signalisation du facteur induit par l'hypoxie HIF-1

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    Menée in vitro et in vivo, cette étude évalue l'activité antitumorale d'une petite molécule inhibitrice de la voie de signalisation du facteur induit par l'hypoxie HIF-1

    “The HIF-pathway inhibitor NSC-134754 induces metabolic changes and anti-tumour activity while maintaining vascular function”

    • Baker, L. C. J.;Boult, J. K. R.;Walker-Samuel, S.;Chung, Y. L.;Jamin, Y.;Ashcroft, M. A.;Robinson, S. P.

    Background: Hypoxia-inducible factor-1 (HIF-1) mediates the transcriptional response to hypoxic stress, promoting tumour progression and survival. This study investigated the acute effects of the small-molecule HIF-pathway inhibitor NSC-134754. Methods: Human PC-3LN5 prostate cancer cells were treated with NSC-134754 for 24 h in hypoxia. Orthotopic prostate tumour-bearing mice were treated with a single dose of NSC-134754 for 6, 24 or 48 h. Treatment response was measured using magnetic resonance spectroscopy and imaging. Ex-vivo histological validation of imaging findings was also sought. Results: In vitro, NSC-134754 significantly reduced lactate production and glucose uptake (P<0.05), while significantly increasing intracellular glucose (P<0.01) and glutamine uptake/metabolism (P<0.05). Increased glutamine metabolism was independent of c-Myc, a factor also downregulated by NSC-134754. In vivo, a significantly higher tumour apparent diffusion coefficient was determined 24 h ...


Mots clés : Prostate; Traitements (Traitements systémiques : découverte et développement)

Mené sur 39 patients atteints d'un cancer du poumon à petites cellules, cet essai de phase II évalue la toxicité et l'efficacité du nativoclax, un inhibiteur de Bcl-2 et Bcl-xL

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    Mené sur 39 patients atteints d'un cancer du poumon à petites cellules, cet essai de phase II évalue la toxicité et l'efficacité du nativoclax, un inhibiteur de Bcl-2 et Bcl-xL

    “Phase 2 Study of Single Agent Navitoclax (ABT-263) and Biomarker Correlates in Patients with Relapsed Small Cell Lung Cancer”

    • Rudin, Charles M.;Hann, Christine L;Garon, Edward B;Ribeiro de Oliveira, Moacyr;Bonomi, Philip D;Camidge, D. Ross;Chu, Quincy;Giaccone, Giuseppe;Khaira, Divis;Ramalingam, Suresh S;Ranson, Malcolm R;Dive, Caroline;McKeegan, Evelyn M;Chyla, Brenda J;Dowell, Barry L;Chakravartty, Arunava;Nolan, Cathy E;Rudersdorf, Niki;Busman, Todd A;Mabry, Mack H;Krivoshik, Andrew P;Humerickhouse, Rod A;Shapiro, Geoffrey I.;Gandhi, Leena

    Purpose: Bcl-2 is a critical regulator of apoptosis that is overexpressed in the majority of small cell lung cancers (SCLC). Nativoclax (ABT-263) is a potent and selective inhibitor of Bcl-2 and Bcl-xL. The primary objectives of this Phase 2a study included safety at the recommended Phase 2 dose and preliminary, exploratory efficacy assessment in patients with recurrent and progressive SCLC after at least one prior therapy. Experimental Design: 39 patients received navitoclax 325mg daily, following an initial lead-in of 150mg daily x 7 days. Study endpoints included safety and toxicity assessment, response rate, progression-free and overall survival (PFS and OS), as well as exploratory pharmacodynamic correlates. Results: The most common toxicity associated with navitoclax was thrombocytopenia, which reached grade 3-4 in 41% of patients. Partial response was observed in one (2.6%) patient and stable disease in 9 (23%). Median PFS was 1.5 months, and median OS 3.2 months. A strong ...


Mots clés : Poumon; Traitements (Traitements systémiques : découverte et développement)

Menée sur des lignées cellulaires de cancer ovarien, cette étude évalue l'intérêt de développer des inhibiteurs de mTOR à large spectre ou des inhibiteurs d'un seul complexe, mTORC1 ou mTORC2

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    Menée sur des lignées cellulaires de cancer ovarien, cette étude évalue l'intérêt de développer des inhibiteurs de mTOR à large spectre ou des inhibiteurs d'un seul complexe, mTORC1 ou mTORC2

    “Predominance of mTORC1 over mTORC2 in the regulation of proliferation of ovarian cancer cells: therapeutic implications”

    • Montero, Juan Carlos;Chen, Xi;Ocana, Alberto;Pandiella, Atanasio

    mTOR is a serine/threonine kinase which acts by binding different sets of proteins forming two complexes, termed mTORC1 and mTORC2. mTOR is deregulated in a substantial proportion of ovarian tumours. Despite the use of drugs directed to mTOR in ongoing clinical trials, the functional relevance of the individual mTORC branches in ovarian cancer is not known. Here we show that mTORC1 and mTORC2 were constitutively active in ovarian cancer cell lines. Knockdown of Raptor or Rictor, proteins required for the function of mTORC1 or mTORC2, respectively, resulted in profound inhibition of ovarian cancer cell proliferation. The knockdown of Raptor had a more important inhibitory effect than the knockdown of Rictor, indicating mTORC1 had a predominant role over mTORC2 in the control of ovarian cancer cell proliferation. Rapamycin decreased the proliferation of ovarian cancer cells, and this was accompanied by inhibition of the phosphorylation of S6, a protein used as readout of mTORC1 ...


Mots clés : Ovaire; Traitements (Traitements systémiques : découverte et développement)

Menée in vitro et à l'aide de xénogreffes, cette étude évalue l'intérêt d'un traitement combinant un composé appelé PF-03084014, un inhibiteur de gamma secrétase, et des glucorticoïdes chez des patients atteints d'un lymphome ou d'une leucémie lymphoblastique aiguë à cellules T

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    Menée in vitro et à l'aide de xénogreffes, cette étude évalue l'intérêt d'un traitement combinant un composé appelé PF-03084014, un inhibiteur de gamma secrétase, et des glucorticoïdes chez des patients atteints d'un lymphome ou d'une leucémie lymphoblastique aiguë à cellules T

    “Preclinical analysis of the gamma-secretase inhibitor PF-03084014 in combination with glucocorticoids in T-cell acute lymphoblastic leukemia”

    • Samon, Jeremy B.;Castillo-Martin, Mireia;Hadler, Michael;Ambesi-Impiombato, Alberto;Paietta, Elisabeth;Racevskis, Janis;Wiernik, Peter H.;Rowe, Jacob M.;Jakubczak, John L.;Randolph, Sophia;Cordon-Cardo, Carlos;Ferrando, Adolfo A.

    T-cell acute lymphoblastic leukemias and lymphomas (T-ALL) are aggressive hematologic cancers frequently associated with activating mutations in NOTCH1. Early studies identified NOTCH1 as an attractive therapeutic target for the treatment of T-ALL through the use of γ-secretase inhibitors (GSIs). Here, we characterized the interaction between PF-03084014, a clinically-relevant GSI, and dexamethasone in preclinical models of glucocorticoid-resistant T-ALL. Combination treatment of the GSI PF-03084014 with glucocorticoids induced a synergistic antileukemic effect in human T-ALL cell lines and primary human T-ALL patient samples. Mechanistically PF-03084014 plus glucocorticoid treatment induced increased transcriptional upregulation of the glucocorticoid receptor and glucocorticoid target genes. Treatment with PF-03084014 and glucocorticoids in combination was highly efficacious in vivo, with enhanced reduction of tumor burden in a xenograft model of T-ALL. Finally, glucocorticoid ...


Mots clés : Leucémie; Traitements (Traitements systémiques : découverte et développement)

Mené sur 15 patients atteints d'une leucémie lymphocytaire chronique, cet essai de phase I évalue une immunothérapie à base d'un adénovirus codant pour la protéine chimérique CD154

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    Mené sur 15 patients atteints d'une leucémie lymphocytaire chronique, cet essai de phase I évalue une immunothérapie à base d'un adénovirus codant pour la protéine chimérique CD154

    “Gene immunotherapy of chronic lymphocytic leukemia: a Phase I study of intranodally injected adenovirus expressing a chimeric CD154 molecule”

    • Castro, Januario E;Melo-Cardenas, Johanna;Urquiza, Mauricio;Barajas-Gamboa, Juan S;Pakbaz, Ramin S;Kipps, Thomas J.

    New therapies for chronic lymphocytic leukemia (CLL) are needed, particularly those that can eradicate residual disease and elicit anti-CLL immune responses. CD40 ligation on CLL cells, which can be achieved using adenovirus encoding chimeric CD154 (Ad-ISF35), enhances their ability to function as antigen presenting cells and increases their sensitivity to clearance by immune-effector mechanisms. In this study, we report the results of a first-in-man Phase I trial of intranodal direct injection (IDI) of Ad-ISF35 in patients with CLL to evaluate toxicity, safety, and tolerability. Fifteen patients received a single IDI of 1-33 x 1010 Ad-ISF35 viral particles (vp), with a defined maximum tolerated dose as 1x1011 vp. Although the most common adverse events were transient grade 1-2 pain at the injection site and flu-like symptoms following IDI, some patients receiving the highest dose had transient, asymptomatic grade 3-4 hypophosphatemia, neutropenia, or transaminitis. Increased ...


Mots clés : Leucémie; Traitements (Traitements systémiques : découverte et développement)

Menée in vitro et in vivo, cette étude suggère que l'inhibition d'une enzyme surexprimée dans les cellules cancéreuses, l'anhydrase carbonique de type IX, augmente l'efficacité du bevacizumab

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    Menée in vitro et in vivo, cette étude suggère que l'inhibition d'une enzyme surexprimée dans les cellules cancéreuses, l'anhydrase carbonique de type IX, augmente l'efficacité du bevacizumab

    “Carbonic anhydrase IX promotes tumour growth and necrosis in vivo and inhibition enhances anti-VEGF therapy”

    • McIntyre, Alan;Patiar, Shalini;Wigfield, Simon;Li, Ji-Liang;Ledaki, Ioanna;Turley, Helen;Leek, Russell;Snell, Cameron;Gatter, Kevin C.;Sly, William S.;Vaughan-Jones, Richard D.;Swietach, Pawel;Harris, Adrian L.

    Purpose:Bevacizumab, an anti-VEGFA antibody, inhibits the developing vasculature of tumours, but resistance is common. Antiangiogenic therapy induces hypoxia and we observed increased expression of hypoxia-regulated genes, including carbonic anhydrase IX (CAIX), in response to Bevacizumab treatment in xenografts. CAIX expression correlates with poor prognosis in most tumour types and with worse outcome in Bevacizumab-treated metastatic colorectal cancer patients, malignant astrocytoma and recurrent malignant glioma. Experimental Design:We knocked-down CAIX expression by shRNA in a colon cancer (HT29) and a glioblastoma (U87) cell line which have high hypoxic-induction of CAIX, and over-expressed CAIX in HCT116 cells which has low CAIX. We investigated the effect on growth rate in 3D culture and in vivo, and examined the effect of CAIX knockdown in combination with Bevacizumab. Results:CAIX expression was associated with increased growth rate in spheroids and in vivo. Surprisingly, ...


Mots clés : Cancer (général); Traitements (Traitements systémiques : découverte et développement)

Menée in vivo et à l'aide d'un modèle mathématique, cette étude évalue la dimension optimale des nanoparticules destinées à pénétrer à l'intérieur des tumeurs

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    Menée in vivo et à l'aide d'un modèle mathématique, cette étude évalue la dimension optimale des nanoparticules destinées à pénétrer à l'intérieur des tumeurs

    “Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner”

    • Chauhan, Vikash P.;Stylianopoulos, Triantafyllos;Martin, John D.;Popovic, Zoran;Chen, Ou;Kamoun, Walid S.;Bawendi, Moungi G.;Fukumura, Dai;Jain, Rakesh K.

    The blood vessels of cancerous tumours are leaky and poorly organized. This can increase the interstitial fluid pressure inside tumours and reduce blood supply to them, which impairs drug delivery. Anti-angiogenic therapies—which ‘normalize’ the abnormal blood vessels in tumours by making them less leaky—have been shown to improve the delivery and effectiveness of chemotherapeutics with low molecular weights, but it remains unclear whether normalizing tumour vessels can improve the delivery of nanomedicines. Here, we show that repairing the abnormal vessels in mammary tumours, by blocking vascular endothelial growth factor receptor-2, improves the delivery of smaller nanoparticles (diameter, 12 nm) while hindering the delivery of larger nanoparticles (diameter, 125 nm). Using a mathematical model, we show that reducing the sizes of pores in the walls of vessels through normalization decreases the interstitial fluid pressure in tumours, thus allowing small nanoparticles to ...


Mots clés : Cancer (général); Traitements (Traitements systémiques : découverte et développement)

Traitements systémiques : applications cliniques

Cet article passe en revue les travaux récents sur le traitement des tumeurs primitives du cerveau chez l'adulte

  • Primary brain tumours in adults
    The Lancet, sous presse, 2012 (résumé)
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    Cet article passe en revue les travaux récents sur le traitement des tumeurs primitives du cerveau chez l'adulte

    “Primary brain tumours in adults”

    • Ricard, Damien;Idbaih, Ahmed;Ducray, François;Lahutte, Marion;Hoang-Xuan, Khê;Delattre, Jean-Yves

    Important advances have been made in the understanding and management of adult gliomas and primary CNS lymphomas?the two most common primary brain tumours. Progress in imaging has led to a better analysis of the nature and grade of these tumours. Findings from large phase 3 studies have yielded some standard treatments for gliomas, and have confirmed the prognostic value of specific molecular alterations. High-throughput methods that enable genome-wide analysis of tumours have improved the knowledge of tumour biology, which should lead to a better classification of gliomas and pave the way for so-called targeted therapy trials. Primary CNS lymphomas are a group of rare non-Hodgkin lymphomas. High-dose methotrexate-based regimens increase survival, but the standards of care and the place of whole-brain radiotherapy remain unclear, and are likely to depend on the age of the patient. The focus now is on the development of new polychemotherapy regimens to reduce or defer whole-brain ...


Mots clés : Système nerveux central; Traitements (Traitements systémiques : applications cliniques)

Cet article passe en revue les travaux récents sur les traitements d'un carcinome métastatique à cellules rénales

  • Treatment selection in metastatic renal cell carcinoma: expert consensus
    Nature Reviews Clinical Oncology, sous presse, 2012 (résumé)
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    Cet article passe en revue les travaux récents sur les traitements d'un carcinome métastatique à cellules rénales

    “Treatment selection in metastatic renal cell carcinoma: expert consensus”

    • Escudier, Bernard;Szczylik, Cezary;Porta, Camillo;Gore, Martin

    In metastatic renal cell carcinoma (mRCC), many factors influence clinical decisions, including histology, tumour burden, prognostic factors, comorbidities, and the ability of the patient to tolerate treatment. Progression-free survival (PFS) durations reported from randomized trials of targeted therapies vary considerably, in part because of differences in patient characteristics. For first-line therapy, an estimate of PFS with sunitinib, bevacizumab plus interferon, or sorafenib in a 'general' population is 8–9 months, but each regimen is suitable for different patient categories. For example, sunitinib is suitable for all-prognosis groups, particularly younger, fitter patients; pazopanib for patients with a good or intermediate prognosis; bevacizumab plus interferon for good-prognosis patients or those with indolent disease; and sorafenib for patients at all prognostic risk levels, particularly the elderly and those with comorbidities. Sequential therapy with targeted agents ...


Mots clés : Rein; Traitements (Traitements systémiques : applications cliniques)

Mené sur 296 patients d'origine est-asiatique atteints d'un cancer avancé du poumon non à petites cellules, cet essai de phase III évalue, du point de vue de la survie sans progression, le gefitinib en traitement d'entretien

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    Mené sur 296 patients d'origine est-asiatique atteints d'un cancer avancé du poumon non à petites cellules, cet essai de phase III évalue, du point de vue de la survie sans progression, le gefitinib en traitement d'entretien

    “Gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-small-cell lung cancer (INFORM; C-TONG 0804): a multicentre, double-blind randomised phase 3 trial”

    • Zhang, Li;Ma, Shenglin;Song, Xiangqun;Han, Baohui;Cheng, Ying;Huang, Cheng;Yang, Shujun;Liu, Xiaoqing;Liu, Yunpeng;Lu, Shun;Wang, Jie;Zhang, Shucai;Zhou, Caicun;Zhang, Xiangwei;Hayashi, Nobuya;Wang, Mengzhao

    Maintenance treatment of patients with advanced non-small-cell lung cancer (NSCLC) without disease progression after first-line chemotherapy is a subject of ongoing research. The aim of the randomised, double-blind, placebo-controlled, INFORM study was to investigate the efficacy, safety, and tolerability of the EGFR-tyrosine-kinase inhibitor gefitinib in the maintenance setting. Patients were aged 18 years or older, were of east Asian ethnic origin, had a life expectancy of more than 12 weeks, histologically or cytologically confirmed stage IIIb or IV NSCLC, a WHO performance status of 0?2, and had completed four cycles of first-line platinum-based doublet chemotherapy without disease progression or unacceptable toxic effects. Between Sept 28, 2008 and Aug 11, 2009, 296 patients were randomly assigned 1:1 to receive either gefitinib (250 mg per day orally) or placebo (orally) within 3?6 weeks after chemotherapy until progression or unacceptable toxic effects. Randomisation was done ...


  • Is benefit of maintenance therapy for NSCLC best defined by progression-free survival?
    The Lancet Oncology, sous presse, 2012 (commentaire en libre accès)
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    Mené sur 296 patients d'origine est-asiatique atteints d'un cancer avancé du poumon non à petites cellules, cet essai de phase III évalue, du point de vue de la survie sans progression, le gefitinib en traitement d'entretien

    “Is benefit of maintenance therapy for NSCLC best defined by progression-free survival?”

    • Reckamp, Karen L.


Mots clés : Poumon; Traitements (Traitements systémiques : applications cliniques)

Menée sur 321 patients atteints d'un myélome multiple et inclus dans un essai de phase III, cette étude compare l'efficacité de deux traitements de consolidation après une greffe autologue de cellules souches hématopoïétiques

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    Menée sur 321 patients atteints d'un myélome multiple et inclus dans un essai de phase III, cette étude compare l'efficacité de deux traitements de consolidation après une greffe autologue de cellules souches hématopoïétiques

    “Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy following autologous hematopoietic stem-cell transplantation in patients with newly diagnosed multiple myeloma”

    • Cavo, Michele;Pantani, Lucia;Petrucci, Maria Teresa;Patriarca, Francesca;Zamagni, Elena;Donnarumma, Daniela;Crippa, Claudia;Boccadoro, Mario;Perrone, Giulia;Falcone, Antonietta;Nozzoli, Chiara;Zambello, Renato;Masini, Luciano;Furlan, Anna;Brioli, Annamaria;Derudas, Daniele;Ballanti, Stelvio;Dessanti, Maria Laura;De Stefano, Valerio;Carella, Angelo Michele;Marcatti, Magda;Nozza, Andrea;Ferrara, Felicetto;Callea, Vincenzo;Califano, Catello;Pezzi, Annalisa;Baraldi, Anna;Grasso, Mariella;Musto, Pellegrino;Palumbo, Antonio

    ABSTRACT In a randomized, phase 3 study, superior complete/near complete response (CR/nCR) rates and extended progression-free survival (PFS) were demonstrated with bortezomib-thalidomide-dexamethasone (VTD) versus thalidomide-dexamethasone (TD) as induction therapy before, and consolidation after, double autotransplantation (ASCT) for newly diagnosed myeloma patients (intention-to-treat analysis; VTD, n=236; TD, n=238). This per-protocol analysis (VTD, n=160; TD, n=161) was aimed to specifically assess the efficacy and safety of consolidation with VTD or TD. Before starting consolidation, CR/nCR rates were not significantly different in the VTD (63.1%) and TD arms (54.7%). After consolidation, CR (60.6% vs. 46.6%) and CR/nCR (73.1% vs. 60.9%) rates were significantly higher for VTD-treated versus TD-treated patients. VTD consolidation significantly increased CR and CR/nCR rates, but TD did not (McNemar's test). With a median follow-up of 30.4 months from start of consolidation, PFS ...


Mots clés : Myélome multiple et maladies immunoprolifératives; Traitements (Traitements systémiques : applications cliniques)

A partir de données portant sur 1 041 patients d'âge inférieur à 18 ans et atteints d'une leucémie lymphoblastique aiguë, cette étude analyse les caractéristiques cliniques associées à l'échec d'une chimiothérapie d'induction

  • Outcomes after Induction Failure in Childhood Acute Lymphoblastic Leukemia
    New England Journal of Medicine, Vol. 366 (15), pp. 1371-1381, 2012 (résumé)
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    A partir de données portant sur 1 041 patients d'âge inférieur à 18 ans et atteints d'une leucémie lymphoblastique aiguë, cette étude analyse les caractéristiques cliniques associées à l'échec d'une chimiothérapie d'induction

    “Outcomes after Induction Failure in Childhood Acute Lymphoblastic Leukemia”

    • Schrappe, Martin;Hunger, Stephen P.;Pui, Ching-Hon;Saha, Vaskar;Gaynon, Paul S.;Baruchel, André;Conter, Valentino;Otten, Jacques;Ohara, Akira;Versluys, Anne Birgitta;Escherich, Gabriele;Heyman, Mats;Silverman, Lewis B.;Horibe, Keizo;Mann, Georg;Camitta, Bruce M.;Harbott, Jochen;Riehm, Hansjörg;Richards, Sue;Devidas, Meenakshi;Zimmermann, Martin

    Background: Failure of remission-induction therapy is a rare but highly adverse event in children and adolescents with acute lymphoblastic leukemia (ALL). Methods: We identified induction failure, defined by the persistence of leukemic blasts in blood, bone marrow, or any extramedullary site after 4 to 6 weeks of remission-induction therapy, in 1041 of 44,017 patients (2.4%) 0 to 18 years of age with newly diagnosed ALL who were treated by a total of 14 cooperative study groups between 1985 and 2000. We analyzed the relationships among disease characteristics, treatments administered, and outcomes in these patients. Results: Patients with induction failure frequently presented with high-risk features, including older age, high leukocyte count, leukemia with a T-cell phenotype, the Philadelphia chromosome, and 11q23 rearrangement. With a median follow-up period of 8.3 years (range, 1.5 to 22.1), the 10-year survival rate (±SE) was estimated at only 32±1%. An age of 10 years or older, ...


  • Attacking Remaining Challenges in Childhood Leukemia
    New England Journal of Medicine, Vol. 366 (15), pp. 1445-1446, 2012 (éditorial)
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    A partir de données portant sur 1 041 patients d'âge inférieur à 18 ans et atteints d'une leucémie lymphoblastique aiguë, cette étude analyse les caractéristiques cliniques associées à l'échec d'une chimiothérapie d'induction

    “Attacking Remaining Challenges in Childhood Leukemia”

    • Rabin, Karen R.


Mots clés : Leucémie; Traitements (Traitements systémiques : applications cliniques)

Menée sur 72 patients atteints d'un cancer colorectal métastatique sans mutation du gène KRAS et traités par irinotecan et cetuximab, cette étude montre que l'expression des kinases AKT et MAPK phosphorylées dans les métastases est associée à la résistance aux anticorps ciblant EGFR

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    Menée sur 72 patients atteints d'un cancer colorectal métastatique sans mutation du gène KRAS et traités par irinotecan et cetuximab, cette étude montre que l'expression des kinases AKT et MAPK phosphorylées dans les métastases est associée à la résistance aux anticorps ciblant EGFR

    “Phosphorylated AKT and MAPK expression in primary tumours and in corresponding metastases and clinical outcome in colorectal cancer patients receiving irinotecan-cetuximab”

    • Scartozzi, Mario;Giampieri, Riccardo;Maccaroni, Elena;Mandolesi, Alessandra;Biagetti, Simona;Alfonsi, Simona;Giustini, Lucio;Loretelli, Cristian;Faloppi, Luca;Bittoni, Alessandro;Bianconi, Maristella;Del Prete, Michela;Bearzi, Italo;Cascinu, Stefano

    BACKGROUND:Clinical observations suggested that a non negligible proportion of patients, ranging from 40% to 70%, does not seem to benefit from the use of anti-EGFR targeted antibodies even in the absence of a mutation of the K- RAS gene. The EGFR pathway activation via the Ras-Raf-MAP-kinase and the protein-serine/threonine kinase AKT could determine resistance to anti-EGFR treatment.METHODS:We tested the interaction between phosphorylated AKT and MAPK expression in colorectal tumours and corresponding metastases and global outcome in K-RAS wild type patients receiving irinotecan-cetuximab.RESULTS:Seventy-two patients with histologically proven metastatic colorectal cancer, treated with Irinotecan and Cetuximab based chemotherapy, were eligible for our analysis. In metastases pAKT correlated with RR (9% vs. 58%, p= 0.004), PFS (2.3 months vs.9.2 months p < 0.0001) and OS (6.1 months vs.26.7 months p < 0.0001) and pMAPK correlated with RR (10% vs., 47%, p = 0.002), PFS (2.3 months ...


Mots clés : Colon-rectum; Traitements (Traitements systémiques : applications cliniques)

Combinaison de traitements localisés et systémiques

A partir de données cliniques provenant de 12 centres américains de greffes d'organes et portant sur 287 patients atteints d'un cholangiocarcinome périhilaire non résécable, cette étude évalue, du point de vue de la survie sans récidive à 5 ans et en fonction des caractéristiques tumorales, l'efficacité d'une chimioradiothérapie néoadjuvante avant une greffe de foie

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    A partir de données cliniques provenant de 12 centres américains de greffes d'organes et portant sur 287 patients atteints d'un cholangiocarcinome périhilaire non résécable, cette étude évalue, du point de vue de la survie sans récidive à 5 ans et en fonction des caractéristiques tumorales, l'efficacité d'une chimioradiothérapie néoadjuvante avant une greffe de foie

    “Efficacy of Neoadjuvant Chemoradiation, followed by Liver Transplantation, for Perihilar Cholangiocarcinoma at 12 US Centers”

    • Murad, Sarwa Darwish;Kim, W. Ray;Harnois, Denise M.;Douglas, David D.;Burton, James;Kulik, Laura M.;Botha, Jean F.;Mezrich, Joshua D.;Chapman, William C.;Schwartz, Jason J.;Hong, Johnny C.;Emond, Jean C.;Jeon, Hoonbae;Rosen, Charles B.;Gores, Gregory J.;Heimbach, Julie K.

    Excellent single-center outcomes of neoadjuvant chemoradiation and liver transplantation for unresectable perihilar cholangiocarcinoma caused the United Network of Organ Sharing (UNOS) to offer a standardized model of end-stage liver disease (MELD) exception for this disease. We analyzed data from multiple centers to determine the effectiveness of this treatment and the appropriateness of the MELD exception. We collected and analyzed data from 12 large-volume transplant centers in the US. These centers met the inclusion criteria of treating 3 or more patients with perihilar cholangiocarcinoma using neoadjuvant therapy, followed by liver transplantation, from 1993 to 2010 (n=287 total patients). Center-specific protocols and medical charts were reviewed on-site. The patients completed external radiation (99%), brachytherapy (75%), radio-sensitizing therapy (98%), and/or maintenance chemotherapy (65%). Seventy-one patients dropped out before liver transplantation (rate of 11.5% in 3 ...


Mots clés : Foie; Traitements (Combinaison de traitements localisés et systémiques)

Mené sur 392 patients atteints d'un cancer rectal localement avancé (âge : 18 ans ou plus ; durée médiane de suivi : 52 mois), cet essai multicentrique de phase 3 compare, du point de vue de la survie globale à 5 ans et des événements indésirables, l'efficacité et la toxicité de deux chimioradiothérapies, l'une par capécitabine et l'autre par fluorouracile

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    Mené sur 392 patients atteints d'un cancer rectal localement avancé (âge : 18 ans ou plus ; durée médiane de suivi : 52 mois), cet essai multicentrique de phase 3 compare, du point de vue de la survie globale à 5 ans et des événements indésirables, l'efficacité et la toxicité de deux chimioradiothérapies, l'une par capécitabine et l'autre par fluorouracile

    “Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial”

    • Hofheinz, Ralf-Dieter;Wenz, Frederik;Post, Stefan;Matzdorff, Axel;Laechelt, Stephan;Hartmann, Jörg T.;Müller, Lothar;Link, Hartmut;Moehler, Markus;Kettner, Erika;Fritz, Elisabeth;Hieber, Udo;Lindemann, Hans Walter;Grunewald, Martina;Kremers, Stephan;Constantin, Christian;Hipp, Matthias;Hartung, Gernot;Gencer, Deniz;Kienle, Peter;Burkholder, Iris;Hochhaus, Andreas

    Fluorouracil-based chemoradiotherapy is regarded as a standard perioperative treatment in locally advanced rectal cancer. We investigated the efficacy and safety of substituting fluorouracil with the oral prodrug capecitabine. This randomised, open-label, multicentre, non-inferiority, phase 3 trial began in March, 2002, as an adjuvant trial comparing capecitabine-based chemoradiotherapy with fluorouracil-based chemoradiotherapy, in patients aged 18 years or older with pathological stage II?III locally advanced rectal cancer from 35 German institutions. Patients in the capecitabine group were scheduled to receive two cycles of capecitabine (2500 mg/m2days 1?14, repeated day 22), followed by chemoradiotherapy (50·4 Gy plus capecitabine 1650 mg/m2days 1?38), then three cycles of capecitabine. Patients in the fluorouracil group received two cycles of bolus fluorouracil (500 mg/m2days 1?5, repeated day 29), followed by chemoradiotherapy (50·4 Gy plus infusional fluorouracil 225 ...


Mots clés : Colon-rectum; Traitements (Combinaison de traitements localisés et systémiques)

A partir des données de deux essais de phase III évaluant un traitement néoadjuvant et incluant 1 767 patients atteints d'un cancer rectal de stade T3-4 (durée médiane de suivi : 5,6 ans), cette étude évalue, du point de vue de la survie globale, du contrôle de la maladie et de la réponse au traitement, l'intérêt d'une chimioradiothérapie pré-opératoire à base de 5-fluorouracile / leucovorine

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    A partir des données de deux essais de phase III évaluant un traitement néoadjuvant et incluant 1 767 patients atteints d'un cancer rectal de stade T3-4 (durée médiane de suivi : 5,6 ans), cette étude évalue, du point de vue de la survie globale, du contrôle de la maladie et de la réponse au traitement, l'intérêt d'une chimioradiothérapie pré-opératoire à base de 5-fluorouracile / leucovorine

    “What is the clinical benefit of preoperative chemoradiotherapy with 5FU/leucovorin for T3-4 rectal cancer in a pooled analysis of EORTC 22921 and FFCD 9203 trials: Surrogacy in question?”

    • Bonnetain, F.;Bosset, J. F.;Gerard, J. P.;Calais, G.;Conroy, T.;Mineur, L.;Bouché, O.;Maingon, P.;Chapet, O.;Radosevic-Jelic, L.;Methy, N.;Collette, L.

    Background : Two phase III trials of neoadjuvant treatment in T3-4 rectal cancer established that adding chemotherapy (CRT) to radiotherapy (RT) improves pathological complete response (pCR) and local control (LC). We combined trials to assess the clinical benefit of CRT on overall (OS) and progression free survival (PFS) and to explore the surrogacy of pCR and LC. Patients and methods : Individual patient data from European Organisation for Research and Treatment of Cancer (EORTC) 22921 (1011 patients) and FFCD 9203 (756 patients) were pooled. Meta-analysis methodology was used to compare neoadjuvant CRT to RT for OS, PFS LC and distant progression (DP). Weighted linear regression was used to estimate trial-level association (surrogacy R2) between treatment effects on candidate surrogate (pCR, LC, DP) and OS. Results : The median follow-up was 5.6 years. Compared to RT (881 pts), CRT (886 pts) did not prolong OS, DP or PFS. The 5-y OS-rate was 66.3% with CRT versus 65.9% in RT ...


Mots clés : Colon-rectum; Traitements (Combinaison de traitements localisés et systémiques)

Ressources et infrastructures (Traitements)

Cet article présente les résumés d'un symposium organisé par une société savante américaine sur l'implication des chercheurs fondamentaux dans les activités de recherche translationnelle

  • Engaging basic scientists in translational research: identifying opportunities, overcoming obstacles
    Journal of Translational Medicine, Vol. 10 (1), pp. 72, 2012 (article en libre accès)
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    Cet article présente les résumés d'un symposium organisé par une société savante américaine sur l'implication des chercheurs fondamentaux dans les activités de recherche translationnelle

    “Engaging basic scientists in translational research: identifying opportunities, overcoming obstacles”

    • Hobin, Jennifer;Deschamps, Anne;Bockman, Richard;Cohen, Stanley;Dechow, Paul;Eng, Charis;Galey, William;Morris, Marianna;Prabhakar, Sharma;Raj, Usha;Rubenstein, Peter;Smith, John;Stover, Patrick;Sung, Nancy;Talman, William;Galbraith, Richard

    This report is based on the Federation of American Societies for Experimental Biology's symposium, "Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles," held in Chevy Chase, MD, March 24-25, 2011. Meeting participants examined the benefits of engaging basic scientists in translational research, the challenges to their participation in translational research, and the roles that research institutions, funding organizations, professional societies, and scientific publishers can play to address these challenges.


Mots clés : Cancer (général); Traitements (Ressources et infrastructures (Traitements))

Signé par des responsables d'autorités réglementaires européennes, cet article analyse les enjeux du libre accès aux données d'essais cliniques

  • Open Clinical Trial Data for All? A View from Regulators
    PLoS Medicine, Vol. 9 (4), pp. e1001202, 2012 (article en libre accès)
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    Signé par des responsables d'autorités réglementaires européennes, cet article analyse les enjeux du libre accès aux données d'essais cliniques

    “Open Clinical Trial Data for All? A View from Regulators”

    • Eichler, Hans-Georg;Abadie, Eric;Breckenridge, Alasdair;Leufkens, Hubert;Rasi, Guido

    Hans-Georg Eichler from the European Medicines Agency and colleagues provide a view from regulators on access to clinical trial data.


Mots clés : Cancer (général); Traitements (Ressources et infrastructures (Traitements))

Cet article passe en revue les perspectives thérapeutiques offertes par le ciblage de protéines impliquées dans la régulation épigénétique de l'expression des gènes

  • Epigenetic protein families: a new frontier for drug discovery
    Nature Reviews Drug Discovery, sous presse, 2012 (résumé)
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    Cet article passe en revue les perspectives thérapeutiques offertes par le ciblage de protéines impliquées dans la régulation épigénétique de l'expression des gènes

    “Epigenetic protein families: a new frontier for drug discovery”

    • Arrowsmith, Cheryl H.;Bountra, Chas;Fish, Paul V.;Lee, Kevin;Schapira, Matthieu

    Epigenetic regulation of gene expression is a dynamic and reversible process that establishes normal cellular phenotypes but also contributes to human diseases. At the molecular level, epigenetic regulation involves hierarchical covalent modification of DNA and the proteins that package DNA, such as histones. Here, we review the key protein families that mediate epigenetic signalling through the acetylation and methylation of histones, including histone deacetylases, protein methyltransferases, lysine demethylases, bromodomain-containing proteins and proteins that bind to methylated histones. These protein families are emerging as druggable classes of enzymes and druggable classes of protein–protein interaction domains. In this article, we discuss the known links with disease, basic molecular mechanisms of action and recent progress in the pharmacological modulation of each class of proteins.


Mots clés : Cancer (général); Traitements (Ressources et infrastructures (Traitements))

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