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Accueil Nota Bene Cancer V2 Numéro 138 du 31 Mai 2012 Traitements

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Nota Bene Cancer Numéro 138 du 31 Mai 2012 RSS

Traitements

Traitements localisés : découverte et développement

Menée sur un modèle murin de carcinome à cellules rénales, cette étude montre qu'une résection tumorale incomplète par cryoablation ou radiofréquences stimule la prolifération des cellules cancéreuses résiduelles

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    Menée sur un modèle murin de carcinome à cellules rénales, cette étude montre qu'une résection tumorale incomplète par cryoablation ou radiofréquences stimule la prolifération des cellules cancéreuses résiduelles

    “Incomplete thermal ablation stimulates proliferation of residual renal carcinoma cells in a translational murine model”

    • Kroeze, Stephanie G. C.;van Melick, Harm H. E.;Nijkamp, Maarten W.;Kruse, Fabian K.;Kruijssen, Laura W. J.;van Diest, Paul J.;Bosch, J. L. H. Ruud;Jans, Judith J. M.

    What's known on the subject? and What does the study add?Thermal ablation influences the local tissue microenvironment. Several studies have reported that residual tumour cells may exhibit a more aggressive phenotype.This study shows that incomplete CA and RFA cause an increased proliferation and decreased apptosis of residual renal tumour cells. This may be caused by stimulatory factors such as hypoxia, HSPs and inflammatory cells. OBJECTIVE * •To compare the effect of incomplete thermal ablation vs partial nephrectomy (PN) on growth stimulation and cellular survival in renal tumours. MATERIALS AND METHODS * •Renca renal tumours were transplanted under the renal capsule of mice (four to six mice/group) after which incomplete radiofrequency ablation (RFA), cryoablation (CA) or PN was performed. * •At several time points after treatment, presence of cell proliferation, apoptosis, hypoxic areas, inflammatory factors and the heat-shock proteins (HSPs) 70 and 90 were evaluated using ...


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

Menée sur des lignées cellulaires de cancer du poumon non à petites cellules, cette étude montre qu'un inhibiteur de l'expression de c-Met, un récepteur à activité tyrosine kinase, sensibilise aux rayonnements ionisants les cellules tumorales exprimant ce récepteur

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    Menée sur des lignées cellulaires de cancer du poumon non à petites cellules, cette étude montre qu'un inhibiteur de l'expression de c-Met, un récepteur à activité tyrosine kinase, sensibilise aux rayonnements ionisants les cellules tumorales exprimant ce récepteur

    “C-Met Inhibitor MK-8003 Radiosensitizes c-Met-Expressing Non-Small-Cell Lung Cancer Cells With Radiation-Induced c-Met-Expression”

    • Bhardwaj, Vikas;Zhan, Yanai;Cortez, Maria Angelica;Ang, Kie Kian;Molkentine, David;Munshi, Anupama;Raju, Uma;Komaki, Ritsuko;Heymach, John V.;Welsh, James

    Introduction: The radiation doses used to treat unresectable lung cancer are often limited by the proximity of normal tissues. Overexpression of c-Met, a receptor tyrosine kinase occurs in about half of non-small-cell lung cancers (NSCLCs) and has been associated with resistance to radiation therapy and poor patient survival. We hypothesized that inhibiting c-Met would increase the sensitivity of NSCLC cells to radiation, enhancing the therapeutic ratio, which may potentially translate into improved local control. Methods: We tested the radiosensitivity of two high-c-Met-expressing NSCLC lines, EBC-1 and H1993, and two low-c-Met-expressing lines, A549 and H460, with and without the small-molecule c-Met inhibitor MK-8033. Proliferation and protein expression were measured with clonogenic survival assays and Western blotting, respectively. [gamma]-H2AX levels were evaluated by immunofluorescence staining. Results: MK-8033 radiosensitized the high-c-Met-expressing EBC-1 and H1993 cells ...


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

Traitements localisés : applications cliniques

Menée sur 400 patients présentant une tumeur rénale traitée entre 2006 et 2011 (âge moyen : 58,5 ans ; durée médiane de suivi : 12,4 mois), cette étude monocentrique analyse les résultats chirurgicaux associés à une néphrectomie partielle laparoscopique assistée par robot

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    Menée sur 400 patients présentant une tumeur rénale traitée entre 2006 et 2011 (âge moyen : 58,5 ans ; durée médiane de suivi : 12,4 mois), cette étude monocentrique analyse les résultats chirurgicaux associés à une néphrectomie partielle laparoscopique assistée par robot

    “Robot-assisted Laparoscopic Partial Nephrectomy: Step-by-step Contemporary Technique and Surgical Outcomes at a Single High-Volume Institution”

    • Jihad, H. Kaouk;Ali, Khalifeh;Shahab, Hillyer;Georges-Pascal, Haber;Robert, J. Stein;Riccardo, Autorino

    Background : Robotic technology is being increasingly adopted in urologic surgery. Objective : To describe a contemporary surgical technique and report cumulative surgical outcomes of robot-assisted laparoscopic partial nephrectomy (RALPN) at our tertiary care institution. Design, setting, and participants : Medical charts of consecutive patients who underwent RALPN between June 2006 and November 2011 were reviewed from a prospectively maintained, institutional review board-approved database. Surgical procedure : The main steps of our current surgical technique are described in this video tutorial: patient positioning and trocar placement; bowel mobilization; hilar dissection; tumor identification and demarcation; clamping of the hilum; tumor excision; renorraphy; hilar unclamping; and tumor retrieval. Outcome measurements and statistical analysis : Patients’ characteristics and main surgical outcomes were analyzed. Results and limitations : A total of 400 patients (mean age: 58.5 ...


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

A partir de données administratives portant sur 1 800 patients atteints d'un carcinome à cellules rénales, cette étude rétrospective analyse leurs caractéristiques cliniques et évalue, du point de vue de la survie spécifique par cancer et par rapport à une métastasectomie pulmonaire (57 cas), l'efficacité d'une intervention chirurgicale pour traiter des métastases atypiques (37 cas)

  • Surgical treatment of atypical metastasis from renal cell carcinoma (RCC)
    BJU International, sous presse, 2012 (résumé)
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    A partir de données administratives portant sur 1 800 patients atteints d'un carcinome à cellules rénales, cette étude rétrospective analyse leurs caractéristiques cliniques et évalue, du point de vue de la survie spécifique par cancer et par rapport à une métastasectomie pulmonaire (57 cas), l'efficacité d'une intervention chirurgicale pour traiter des métastases atypiques (37 cas)

    “Surgical treatment of atypical metastasis from renal cell carcinoma (RCC)”

    • Antonelli, Alessandro;Arrighi, Nicola;Corti, Serena;Legramanti, Stefano;Zanotelli, Tiziano;Cozzoli, Alberto;Cunico, Sergio Cosciani;Simeone, Claudio

    OBJECTIVE : To review the clinical characteristics and oncological results in patients submitted to surgical removal of metastasis from renal cell carcinoma (RCC) in atypical sites (atypical metastasis [AM], i.e. metastasis in sites other than the chest, liver, bone, adrenal, brain, kidney, and lymph nodes), compared with patients submitted to metastasectomy due to a lung metastasis (LM). PATIENTS AND METHODS : From an institutional database of ≈1800 patients surgically treated for a RCC, we retrospectively identified 37 cases that had undergone metastasectomy for AM and 57 operated for LM. Clinicopathological features of the primary RCC and metastasis, and cancer-specific survival (CSS) computed from the time of metastasectomy of patients with AM and LM, were compared. A univariate and multivariable analysis applying a Cox regression model was used to evaluate CSS. RESULTS : The patients with AM and LM were followed for an average of 40.8 and 50.7 months from metastasectomy, ...


Mots clés : Cancer (général); Traitements (Traitements localisés : applications cliniques)

Traitements systémiques : découverte et développement

Menée in vitro et in vivo, cette étude suggère que la petite molécule RITA est susceptible de restaurer la fonction de suppresseur de tumeurs de p53 et, ainsi, d'augmenter l'efficacité du cisplatine dans le traitement des cancers de la tête et du cou

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    Menée in vitro et in vivo, cette étude suggère que la petite molécule RITA est susceptible de restaurer la fonction de suppresseur de tumeurs de p53 et, ainsi, d'augmenter l'efficacité du cisplatine dans le traitement des cancers de la tête et du cou

    “The p53-reactivating small-molecule RITA enhances cisplatin-induced cytotoxicity and apoptosis in head and neck cancer”

    • Roh, Jong-Lyel;Ko, Jung Ho;Moon, Soo Jin;Ryu, Chang Hwan;Choi, Jun Young;Koch, Wayne M.

    We evaluated whether the restoration of p53 function by the p53-reactivating small molecule RITA (reactivation of p53 and induction of tumor cell apoptosis enhances cisplatin-induced cytotoxicity and apoptosis in head-and-neck cancer (HNC). RITA induced prominent accumulation and reactivation of p53 in a wild-type TP53-bearing HNC cell line. RITA showed maximal growth suppression in tumor cells showing MDM2-dependent p53 degradation. RITA promoted apoptosis in association with upregulation of p21, BAX, and cleaved caspase-3; notably, the apoptotic response was blocked by pifithrin-α, demonstrating its p53 dependence. With increasing concentrations, RITA strongly induced apoptosis rather than G2-phase arrest. In combination therapy, RITA enhanced cisplatin-induced growth inhibition and apoptosis of HNC cells in vitro and in vivo. Our data suggest that the restoration of p53 tumor-suppressive function by RITA enhances the cytotoxicity and apoptosis of cisplatin, an action that may ...


Mots clés : Voies aérodigestives supérieures; Traitements (Traitements systémiques : découverte et développement)

Menée sur des lignées cellulaires et à l'aide d'un modèle murin, cette étude suggère que des antagonistes du récepteur CCR5 pourraient être utlisés en traitement adjuvant chez les patientes atteintes d'un cancer du sein de type basal

  • CCR5 antagonist blocks metastasis of basal breast cancer cells
    Cancer Research, sous presse, 2012 (résumé)
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    Menée sur des lignées cellulaires et à l'aide d'un modèle murin, cette étude suggère que des antagonistes du récepteur CCR5 pourraient être utlisés en traitement adjuvant chez les patientes atteintes d'un cancer du sein de type basal

    “CCR5 antagonist blocks metastasis of basal breast cancer cells”

    • Velasco-Velazquez, Marco;Jiao, Xuanmao;De La Fuente, Marisol;Pestell, Timothy G.;Ertel, Adam;Lisanti, Michael P.;Pestell, Richard G.

    The roles of the chemokine CCL5 and its receptor CCR5 in breast cancer progression remain unclear. Here we performed microarray analysis on 2,254 human breast cancer specimens and found increased expression of CCL5 and its receptor CCR5, but not CCR3, in the basal and HER-2 genetic subtypes. The subpopulation of human breast cancer cell lines found to express CCR5 displayed a functional response to CCL5. In addition, oncogene transformation induced CCR5 expression, and the subpopulation of cells that expressed functional CCR5 also displayed increased invasiveness. The CCR5 antagonists Maraviroc or Vicriviroc, developed to block CCR5 HIV co-receptor function, reduced in vitro invasion of basal breast cancer cells without affecting cell proliferation or viability, and Maraviroc decreased pulmonary metastasis in a preclinical mouse model of breast cancer. Taken together, our findings provide evidence for the key role of CCL5/CCR5 in the invasiveness of basal breast cancer cells and ...


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

Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude évalue les perspectives offertes par le panobinostat, un inhibiteur d'histone déacétylase, pour le traitement d'un cancer du sein triplement négatif

  • Targeting triple-negative breast cancer cells with the HDAC inhibitor Panobinostat
    Breast Cancer Research, Vol. 14 (3), pp. R79, 2012 (article en libre accès)
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    Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude évalue les perspectives offertes par le panobinostat, un inhibiteur d'histone déacétylase, pour le traitement d'un cancer du sein triplement négatif

    “Targeting triple-negative breast cancer cells with the HDAC inhibitor Panobinostat”

    • Tate, Chandra;Rhodes, Lyndsay;Segar, H;Driver, Jennifer;Pounder, F;Burow, Matthew;Collins-Burow, Bridgette

    INTRODUCTION:Of the more than one million global cases of breast cancer diagnosed each year, approximately fifteen percent are characterized as triple-negative, lacking the estrogen, progesterone, and Her2/neu receptors. Lack of effective therapies, younger age at onset, and early metastatic spread have contributed to the poor prognoses and outcomes associated with these malignancies. Here, we investigate the ability of the histone deacetylase inhibitor panobinostat (LBH589) to selectively target triple-negative breast cancer (TNBC) cell proliferation and survival in vitro and tumorigenesis in vivo.METHODS:TNBC cell lines MDA-MB-157, MDA-MB-231, MDA-MB-468, and BT-549 were treated with nanomolar (nM) quantities of panobinostat. Relevant histone acetylation was verified by flow cytometry and immunofluorescent imaging. Assays for trypan blue viability, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) proliferation, and DNA fragmentation were used to evaluate overall ...


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

Mené sur un modèle murin, cette étude montre qu'un composé apparenté à la famille des taxanes (TPI-287) est susceptible de franchir la barrière hémato-encéphalique et de prévenir la formation de métastases cérébrales d'un cancer du sein

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    Mené sur un modèle murin, cette étude montre qu'un composé apparenté à la famille des taxanes (TPI-287) est susceptible de franchir la barrière hémato-encéphalique et de prévenir la formation de métastases cérébrales d'un cancer du sein

    “TPI-287, a new taxane family member, reduces the brain metastatic colonization of breast cancer cells”

    • Fitzgerald, Daniel P;Emerson, David L;Qian, Yongzhen;Anwar, Talha;Liewehr, David J;Steinberg, Seth M.;Silberman, Sandra;Palmieri, Diane;Steeg, Patricia S

    Brain metastases of breast and other cancers remain resistant to chemotherapeutic regimens that are effective systemically, in part due to the blood-brain barrier. We report that TPI-287, a new microtubule stabilizing agent, displays in vitro cytotoxic activity similar to taxanes and epothilones. Unlike the taxanes, TPI-287 is permeable through the blood-brain barrier. Brain-to-plasma ratios of TPI-287 after a single injection typically exceeded 1 and were as high as 63.8 in the rat and 14.1 in the mouse. A brain-tropic derivative of the MDA-MB-231 "triple negative" breast cancer cell line, 231-BR, was used to test whether TPI-287 may be efficacious at preventing or treating brain metastases. TPI-287 had growth inhibitory effects comparable to paclitaxel when 231-BR tumor cells were injected into the mammary fat pad. Brain metastatic colonization was determined by intracardiac injection of 231-BR cells, with treatment beginning on day 3-4 post-injection, culminating in a histologic ...


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

Menée sur divers modèles murins de cancer du sein, cette étude met en évidence un mécanisme par lequel la ligase Skp2, en régulant l'activation de la kinase Akt, favorise le processus métastatique d'un cancer du sein HER2+

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    Menée sur divers modèles murins de cancer du sein, cette étude met en évidence un mécanisme par lequel la ligase Skp2, en régulant l'activation de la kinase Akt, favorise le processus métastatique d'un cancer du sein HER2+

    “The Skp2-SCF E3 Ligase Regulates Akt Ubiquitination, Glycolysis, Herceptin Sensitivity, and Tumorigenesis”

    • Chan, Chia-Hsin;Li, Chien-Feng;Yang, Wei-Lei;Gao, Yuan;Lee, Szu-Wei;Feng, Zizhen;Huang, Hsuan-Ying;Tsai, Kelvin K C.;Flores, Leo G;Shao, Yiping;Hazle, John D;Yu, Dihua;Wei, Wenyi;Sarbassov, Dos;Hung, Mien-Chie;Nakayama, Keiichi I;Lin, Hui-Kuan

    Akt kinase plays a central role in cell growth, metabolism, and tumorigenesis. The TRAF6 E3 ligase orchestrates IGF-1-mediated Akt ubiquitination and activation. Here, we show that Akt ubiquitination is also induced by activation of ErbB receptors; unexpectedly, and in contrast to IGF-1 induced activation, the Skp2 SCF complex, not TRAF6, is a critical E3 ligase for ErbB-receptor-mediated Akt ubiquitination and membrane recruitment in response to EGF. Skp2 deficiency impairs Akt activation, Glut1 expression, glucose uptake and glycolysis, and breast cancer progression in various tumor models. Moreover, Skp2 overexpression correlates with Akt activation and breast cancer metastasis and serves as a marker for poor prognosis in Her2-positive patients. Finally, Skp2 silencing sensitizes Her2-overexpressing tumors to Herceptin treatment. Our study suggests that distinct E3 ligases are utilized by diverse growth factors for Akt activation and that targeting glycolysis sensitizes ...


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

Cet article passe en revue les travaux récents sur le rôle fonctionnel des micro-ARNs dans la réponse aux traitements du cancer de la prostate

  • MicroRNAs as putative mediators of treatment response in prostate cancer
    Nature Reviews Urology, sous presse, 2012 (résumé)
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    Cet article passe en revue les travaux récents sur le rôle fonctionnel des micro-ARNs dans la réponse aux traitements du cancer de la prostate

    “MicroRNAs as putative mediators of treatment response in prostate cancer”

    • O'Kelly, Fardod;Marignol, Laure;Meunier, Armelle;Lynch, Thomas H.;Perry, Antoinette S.;Hollywood, Donal

    MicroRNAs (miRNAs) are an abundant class of noncoding RNAs that function to regulate post-transcriptional gene expression, predominantly by translational repression. In addition to their role in prostate cancer initiation and progression, recent evidence suggests that miRNAs might also participate in treatment response across a range of therapies including radiation treatment, chemotherapy and androgen suppression. The mechanism of this regulation is thought to be multifactorial and is currently poorly understood. To date, only a small number of studies have examined the functional role of miRNAs in response to prostate cancer treatment. Elucidating the role of miRNAs in treatment response following radiotherapy, chemotherapy and androgen suppression will provide new avenues of investigation for the development of novel therapies for the treatment of prostate cancer.


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

Menée sur des lignées cellulaires d'adénocarcinome canalaire du pancréas, cette étude évalue l'activité antitumorale d'un traitement combinant un inhibiteur d'une molécule jouant un rôle essentiel dans les cellules souches cancéreuses, EZH2, et la gemcitabine

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    Menée sur des lignées cellulaires d'adénocarcinome canalaire du pancréas, cette étude évalue l'activité antitumorale d'un traitement combinant un inhibiteur d'une molécule jouant un rôle essentiel dans les cellules souches cancéreuses, EZH2, et la gemcitabine

    “Molecular mechanisms involved in the synergistic interaction of the EZH2 inhibitor 3-deazaneplanocin A (DZNeP) with gemcitabine in pancreatic cancer cells”

    • Avan, Amir;Crea, Francesco;Paolicchi, Elisa;Funel, Niccola;Galvani, Elena;Marquez, Victor E.;Honeywell, Richard J.;Danesi, Romano;Peters, Godefridus J.;Giovannetti, Elisa

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by overexpression of Enhancer-of Zeste-Homolog-2 (EZH2), which plays a pivotal role in cancer-stem-cell (CSC) self-renewal through methylation of histone-H3-lysine-27 (H3K27m3). Against this background, EZH2 was identified as an attractive target and we investigated the interaction of the EZH2-inhibitor DZNeP with gemcitabine. EZH2 expression was detected by quantitative-RT-PCR in 15 PDAC cells, including 7 primary cell cultures, showing expression values correlated with their originator tumors (Spearman-R2=0.89, P=0.01). EZH2 expression in cancer cells was significantly higher than in normal ductal pancreatic cells and fibroblasts. DZNeP (5 µM, 72-hour-exposure) modulated EZH2 and H3K27m3 protein expression, and synergistically enhanced the antiproliferative activity of gemcitabine, with combination index values of 0.2 (PANC-1), 0.3 (MIA-PaCa-2) and 0.7 (LPC006). The drug combination reduced the percentages of cells in G2/M ...


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

Cet article passe en revue les voies de signalisation du micro-environnement tumoral impliquées dans l'apparition d'une résistance à un traitement anticancéreux

  • Molecular Pathways Involving Microenvironment Damage Responses in Cancer Therapy Resistance
    Clinical Cancer Research, sous presse, 2012 (résumé)
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    Cet article passe en revue les voies de signalisation du micro-environnement tumoral impliquées dans l'apparition d'une résistance à un traitement anticancéreux

    “Molecular Pathways Involving Microenvironment Damage Responses in Cancer Therapy Resistance”

    • Sun, Yu;Nelson, Peter S.

    The armamentarium of therapeutics used to treat cancer patients relies heavily on ionizing radiation and chemotherapeutic drugs that severely damage DNA. The responses of tumor cells to these treatments is heavily influenced by their environment: physical contacts with structural elements such as extracellular matrix, associations with resident and transitory benign cells such as fibroblasts and leukocytes, and interactions with numerous soluble endocrine and paracrine-acting factors all modulate tumor cell behavior. Importantly, this complex tumor microenvironment is not static and dynamically responds to a variety of stimuli. Here, we describe emerging data indicating that genotoxic cancer treatments activate highly conserved damage response programs in benign constituents of the tumor microenvironment. These damage signals, transmitted via master regulators such as NFkB, culminate in a powerful and diverse secretory program that generates a pro-angiogenic, pro-inflammatory ...


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

Menée in vitro et in vivo, cette étude suggère que la thioridazine, un médicament antipsychotique, est susceptible d'interagir de façon sélective avec les récepteurs à la dopamine présents à la surface des cellules souches de leucémie et de cancer du sein

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    Menée in vitro et in vivo, cette étude suggère que la thioridazine, un médicament antipsychotique, est susceptible d'interagir de façon sélective avec les récepteurs à la dopamine présents à la surface des cellules souches de leucémie et de cancer du sein

    “Identification of Drugs Including a Dopamine Receptor Antagonist that Selectively Target Cancer Stem Cells”

    • Sachlos, Eleftherios;Risueño, Ruth M;Laronde, Sarah;Shapovalova, Zoya;Lee, Jong-Hee;Russell, Jennifer;Malig, Monika;McNicol, Jamie D;Fiebig-Comyn, Aline;Graham, Monica;Levadoux-Martin, Marilyne;Lee, Jung Bok;Giacomelli, Andrew O;Hassell, John A;Fischer-Russell, Daniela;Trus, Michael R;Foley, Ronan;Leber, Brian;Xenocostas, Anargyros;Brown, Eric D;Collins, Tony J;Bhatia, Mickie

    Selective targeting of cancer stem cells (CSCs) offers promise for a new generation of therapeutics. However, assays for both human CSCs and normal stem cells that are amenable to robust biological screens are limited. Using a discovery platform that reveals differences between neoplastic and normal human pluripotent stem cells (hPSC), we identify small molecules from libraries of known compounds that induce differentiation to overcome neoplastic self-renewal. Surprisingly, thioridazine, an antipsychotic drug, selectively targets the neoplastic cells, and impairs human somatic CSCs capable of in vivo leukemic disease initiation while having no effect on normal blood SCs. The drug antagonizes dopamine receptors that are expressed on CSCs and on breast cancer cells as well. These results suggest that dopamine receptors may serve as a biomarker for diverse malignancies, demonstrate the utility of using neoplastic hPSCs for identifying CSC-targeting drugs, and provide support for the use ...


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

Mené sur un modèle murin et à l'aide de xénogreffes, cette étude montre qu'un peptide (BIM SAHB A ) est susceptible de réactiver une voie de signalisation de l'apoptose dans les cellules de cancers hématologiques

  • A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers
    The Journal of Clinical Investigation, sous presse, 2012 (article en libre accès)
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    Mené sur un modèle murin et à l'aide de xénogreffes, cette étude montre qu'un peptide (BIM SAHB A ) est susceptible de réactiver une voie de signalisation de l'apoptose dans les cellules de cancers hématologiques

    “A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers”

    • LaBelle, James L.;Katz, Samuel G.;Bird, Gregory H.;Gavathiotis, Evripidis;Stewart, Michelle L.;Lawrence, Chelsea;Fisher, Jill K.;Godes, Marina;Pitter, Kenneth;Kung, Andrew L.;Walensky, Loren D.

    Cancer cells subvert the natural balance between cellular life and death, achieving immortality through pathologic enforcement of survival pathways and blockade of cell death mechanisms. Pro-apoptotic BCL-2 family proteins are frequently disarmed in relapsed and refractory cancer through genetic deletion or interaction-based neutralization by overexpressed antiapoptotic proteins, resulting in resistance to chemotherapy and radiation treatments. New pharmacologic strategies are urgently needed to overcome these formidable apoptotic blockades. We harnessed the natural killing activity of BCL-2–interacting mediator of cell death (BIM), which contains one of the most potent BH3 death domains of the BCL-2 protein family, to restore BH3-dependent cell death in resistant hematologic cancers. A hydrocarbon-stapled peptide modeled after the BIM BH3 helix broadly targeted BCL-2 family proteins with high affinity, blocked inhibitory antiapoptotic interactions, directly triggered proapoptotic ...


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

Traitements systémiques : applications cliniques

Mené sur 110 patientes atteintes d'un cancer du sein HER2+ métastatique et ayant reçu divers traitements préalables, cet essai de phase II évalue, du point de vue du taux de réponse globale, un conjugué anticorps-médicament, le trastuzumab-emtansine (T-DM1)

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    Mené sur 110 patientes atteintes d'un cancer du sein HER2+ métastatique et ayant reçu divers traitements préalables, cet essai de phase II évalue, du point de vue du taux de réponse globale, un conjugué anticorps-médicament, le trastuzumab-emtansine (T-DM1)

    “A Phase II Study of Trastuzumab Emtansine in Patients With Human Epidermal Growth Factor Receptor 2 –Positive Metastatic Breast Cancer Who Were Previously Treated With Trastuzumab, Lapatinib, an Anthracycline, a Taxane, and Capecitabine”

    • Krop, Ian E.;LoRusso, Patricia;Miller, Kathy D.;Modi, Shanu;Yardley, Denise;Rodriguez, Gladys;Guardino, Ellie;Lu, Michael;Zheng, Maoxia;Girish, Sandhya;Amler, Lukas;Winer, Eric P.;Rugo, Hope S.

    Purpose To determine whether the antibody-drug conjugate trastuzumab emtansine (T-DM1), which combines human epidermal growth factor receptor 2 (HER2) –targeted delivery of the potent antimicrotubule agent DM1 with the antitumor activity of trastuzumab, is effective in patients with HER2-positive metastatic breast cancer (MBC) who have previously received all standard HER2-directed therapies.Patients and methods In this single-arm phase II study, T-DM1 3.6 mg/kg was administered intravenously every 3 weeks to patients with HER2-positive MBC who had prior treatment with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. The primary objectives were overall response rate (ORR) by independent review and safety.Results Among 110 pretreated patients (median, seven prior agents for MBC; median follow-up, 17.4 months), the ORR was 34.5% (95% CI, 26.1% to 43.9%), clinical benefit rate was 48.2% (95% CI, 38.8% to 57.9%), median progression-free survival (PFS) was 6.9 months ...


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

Menée sur une vaste cohorte de patientes ayant été traitées pour un cancer du sein entre 1998 et 2009 aux Etats-Unis, cette étude analyse l'évolution de l'usage de chimiothérapies à base de taxanes et d'anthracyclines

  • Decline in the Use of Anthracyclines for Breast Cancer
    Journal of Clinical Oncology, sous presse, 2012 (résumé)
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    Menée sur une vaste cohorte de patientes ayant été traitées pour un cancer du sein entre 1998 et 2009 aux Etats-Unis, cette étude analyse l'évolution de l'usage de chimiothérapies à base de taxanes et d'anthracyclines

    “Decline in the Use of Anthracyclines for Breast Cancer”

    • Giordano, Sharon H.;Lin, Yu-Li;Kuo, Yong Fang;Hortobagyi, Gabriel N.;Goodwin, James S.

    Purpose To determine the patterns of use of anthracycline- and taxane-based chemotherapy for breast cancer treatment.Methods Claims from a 5% national Medicare sample and from a nationally representative claims database (Marketscan) from 1998 to 2009 were used. Patients with International Classification of Diseases (ICD), ninth revision, codes indicating breast cancer, ICD and Common Procedural Terminology codes indicating breast surgery, and claims for chemotherapy between 3 months before and 12 months after surgery comprised the study cohort. Chemotherapy was classified as anthracycline-based or taxane-based, and the percentages of use were calculated. Piecewise regression models were used to identify the inflection points in the rates of chemotherapy use. The effect of patient characteristics on receiving different types of chemotherapy was estimated by multivariable logistic regression models.Results A total of 4,458 patients were included in the Medicare cohort and 30,422 in the ...


  • Choosing the Best Trastuzumab-Based Adjuvant Chemotherapy Regimen: Should We Abandon Anthracyclines?
    Journal of Clinical Oncology, sous presse, 2012 (commentaire en libre accès)
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    Menée sur une vaste cohorte de patientes ayant été traitées pour un cancer du sein entre 1998 et 2009 aux Etats-Unis, cette étude analyse l'évolution de l'usage de chimiothérapies à base de taxanes et d'anthracyclines

    “Choosing the Best Trastuzumab-Based Adjuvant Chemotherapy Regimen: Should We Abandon Anthracyclines?”

    • Burstein, Harold J. ; Piccart-Gebhart, Martine J. ; Perez, Edith A. ; Hortobagyi, Gabriel N. ; Wolmark, Norman ; Albain, Kathy S. ; Norton, Larry ; Winer, Eric P. ; Hudis, Clifford A.


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

Mené sur 119 patientes atteintes d'un cancer du sein de stade II/III, cet essai évalue, du point de vue de la survie sans maladie et de la survie globale, l'ajout d'acide zolédronique à une chimiothérapie adjuvante (durée médiane de suivi : 61,9 mois)

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    Mené sur 119 patientes atteintes d'un cancer du sein de stade II/III, cet essai évalue, du point de vue de la survie sans maladie et de la survie globale, l'ajout d'acide zolédronique à une chimiothérapie adjuvante (durée médiane de suivi : 61,9 mois)

    “Effect of (Neo)adjuvant zoledronic acid on disease-free and overall survival in clinical stage II/III breast cancer”

    • Aft, R. L.;Naughton, M.;Trinkaus, K.;Weilbaecher, K.

    Background: Despite neoadjuvant/adjuvant chemotherapy, women with resectable stage II/III breast cancer (BC) have high risk of recurrent disease. Recent data suggest that zoledronic acid (ZOL) therapy concurrent with adjuvant treatments may improve cancer-related outcomes in patients with BC. Methods: Disease-free survival (DFS; secondary end point) and overall survival (OS; tertiary end point) were evaluated in 119 women with stage II/III BC randomised to intravenous ZOL 4 mg every 3 weeks for 1 year or no ZOL (control) starting with the first chemotherapy cycle. Results: At 61.9 months’ median follow-up, there was no significant difference in recurrence or survival between study arms. However, time to recurrence or death (DFS) was significantly different between subgroups defined by oestrogen receptor (ER) status (interaction P=0.010 for DFS and 0.025 for OS). Hazard ratios (HRs) for disease recurrence and death were significantly less among patients with ER-negative (ER−) ...


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

Cet article passe en revue les travaux récents sur le rôle des inhibiteurs du protéasome dans le traitement d'un myélome multiple

  • Proteasome inhibitors in multiple myeloma: ten years later
    Blood, sous presse, 2012 (résumé)
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    Cet article passe en revue les travaux récents sur le rôle des inhibiteurs du protéasome dans le traitement d'un myélome multiple

    “Proteasome inhibitors in multiple myeloma: ten years later”

    • Moreau, Philippe;Richardson, Paul G.;Cavo, Michele;Orlowski, Robert Z.;San Miguel, Jesús F.;Palumbo, Antonio;Harousseau, Jean-Luc

    Proteasome inhibition has emerged as an important therapeutic strategy in multiple myeloma (MM). Since the publication of the first phase 1 trials of bortezomib 10 years ago, this first-in-class proteasome inhibitor (PI) has contributed substantially to the observed improvement in survival in MM patients over the past decade. Although first approved as a single agent in the relapsed setting, bortezomib is now predominantly used in combination regimens. Furthermore, the standard twice-weekly schedule may be replaced by weekly infusion, especially when bortezomib is used as part of combination regimens in frontline therapy. Indeed, bortezomib is an established component of induction therapy for patients eligible or ineligible for autologous stem cell transplantation (ASCT). Bortezomib has also been incorporated into conditioning regimens prior to ASCT, as well as into post-ASCT consolidation therapy, and in the maintenance setting. Additionally, a new route of bortezomib administration, ...


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

Cet article passe en revue les travaux récents sur l'efficacité et la toxicité d'un traitement combinant lénalidomide et dexaméthasone chez les patients atteints d'un myélome multiple et présentant une insuffisance rénale

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    Cet article passe en revue les travaux récents sur l'efficacité et la toxicité d'un traitement combinant lénalidomide et dexaméthasone chez les patients atteints d'un myélome multiple et présentant une insuffisance rénale

    “Treatment with lenalidomide and dexamethasone in patients with multiple myeloma and renal impairment”

    • Dimopoulos, Meletios A.;Terpos, Evangelos;Goldschmidt, Hartmut;Alegre, Adrian;Mark, Tomer;Niesvizky, Ruben

    Renal impairment (RI) is a common complication affecting patients with multiple myeloma (MM). Timely identification of MM-related RI and early treatment with novel antimyeloma agents can reverse renal damage in a high proportion of patients and improve outcomes. The IMiDs® immunomodulatory compound lenalidomide (Len) in combination with dexamethasone (Dex) is an effective and well-tolerated regimen for patients with relapsed or refractory (RR) MM. A retrospective analysis of Phase III data has shown that Len/Dex remains effective and well-tolerated in patients with moderate or severe RI, albeit with an increase in myelosuppression. This analysis demonstrated that in a high proportion of patients Len/Dex treatment can reverse MM-related RI and restore normal function. Lenalidomide has a predominantly renal route of excretion and in patients with RI the plasma concentration and half-life of the drug are significantly increased. As a consequence, lower starting doses are required in ...


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

Mené dans 66 hôpitaux sur 140 patients atteints d'un lymphome non hodgkinien agressif, réfractaire ou récidivant, cet essai international évalue l'efficacité et la toxicité du pixantrone en traitement de rattrapage

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    Mené dans 66 hôpitaux sur 140 patients atteints d'un lymphome non hodgkinien agressif, réfractaire ou récidivant, cet essai international évalue l'efficacité et la toxicité du pixantrone en traitement de rattrapage

    “Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial”

    • Pettengell, Ruth;Coiffier, Bertrand;Narayanan, Geetha;de Mendoza, Fernando Hurtado;Digumarti, Raghunadharao;Gomez, Henry;Zinzani, Pier Luigi;Schiller, Gary;Rizzieri, David;Boland, Giles;Cernohous, Paul;Wang, Lixia;Kuepfer, Christine;Gorbatchevsky, Igor;Singer, Jack W.

    Pixantrone dimaleate (pixantrone)?a novel aza-anthracenedione?was synthesised to reduce anthracycline-related cardiotoxicity without compromising antitumour efficacy. We aimed to assess the efficacy and safety of pixantrone versus an investigator's choice of a single-agent therapy in heavily pretreated patients with relapsed or refractory aggressive non-Hodgkin lymphoma. In this phase 3, multicentre, open-label, randomised trial at 66 hospitals in Europe, India, Russia, South America, the UK, and the USA, patients with histologically confirmed aggressive non-Hodgkin lymphoma who had relapsed after two or more previous chemotherapy regimens were randomly assigned (1:1) by an interactive voice response system to treatment with pixantrone dimaleate (85 mg/m2intravenously on days 1, 8, and 15 of a 28-day cycle, for up to six cycles) or to a comparator (vinorelbine, oxaliplatin, ifosfamide, etoposide, mitoxantrone, or gemcitabine) given at prespecified standard doses and schedules. ...


  • Pixantrone: a new agent for relapsed aggressive lymphomas
    The Lancet Oncology, sous presse, 2012 (commentaire en libre accès)
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    Mené dans 66 hôpitaux sur 140 patients atteints d'un lymphome non hodgkinien agressif, réfractaire ou récidivant, cet essai international évalue l'efficacité et la toxicité du pixantrone en traitement de rattrapage

    “Pixantrone: a new agent for relapsed aggressive lymphomas”

    • Cabanillas, Fernando

    Pixantrone, an anthracycline with a novel chemical structure, was synthesised about 20 years ago to provide similar antitumour activity to the anthracyclines, but without the cardiotoxicity. In March 22, 2010, the drug underwent review by the Oncologic Drugs Advisory Committee of the US Food and Drug Administration (FDA), and was promptly rejected. In spite of the FDA's rejection in the USA, the European Medicines Agency (EMA) granted the drug approval in February, 2012, on the condition that additional data for patients who had previously received rituximab be provided in the future. Now that the storm has passed—2 years after the controversial FDA rejection and a few months after EMA's conditional approval—the full results of the study have been published in The Lancet Oncology.


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

A partir de données portant sur 33 574 patients inclus dans des essais cliniques de traitement adjuvant d'un cancer du côlon de stade II ou III, cette étude évalue les bénéfices et les effets indésirables des traitements en fonction de l'âge des patients

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    A partir de données portant sur 33 574 patients inclus dans des essais cliniques de traitement adjuvant d'un cancer du côlon de stade II ou III, cette étude évalue les bénéfices et les effets indésirables des traitements en fonction de l'âge des patients

    “Benefits and Adverse Events in Younger Versus Older Patients Receiving Adjuvant Chemotherapy for Colon Cancer: Findings From the Adjuvant Colon Cancer Endpoints Data Set”

    • Hubbard, Joleen;Thomas, David M.;Yothers, Greg;Green, Erin;Blanke, Charles;O'Connell, Michael J.;Labianca, Roberto;Shi, Qian;Bleyer, Archie;de Gramont, Aimery;Sargent, Daniel

    Purpose Limited data exist regarding the outcomes of adjuvant therapy in younger patients with stage II and III colon cancer. We examined disease-free survival (DFS), overall survival (OS), recurrence-free interval (RFI), and grade 3+ adverse events (AEs) in younger patients in the 33,574 patient Adjuvant Colon Cancer Endpoints Group data set.Patients and Methods Individual patient data from 24 randomized phase III clinical trials were obtained for survival outcomes, which included 10 clinical trials for AE outcomes. Two age-based cutoff points were used to define younger patients: age younger than 40 years and younger than 50 years. Adjuvant therapy benefit analyses were limited to the nine clinical trials in which the investigational chemotherapeutic arm demonstrated benefit.Results One thousand seven hundred fifty-eight patients (5.2%) were younger than 40 years, 5,817 patients (17.3%) were younger than 50 years, and only 299 patients (0.9%) were younger than 30 years. No ...


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

Mené sur 34 patients atteints d'une tumeur stromale gastrointestinale métastatique, cet essai de phase II évalue le regorafenib après l'échec d'un traitement par imatinib ou sunitinib

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    Mené sur 34 patients atteints d'une tumeur stromale gastrointestinale métastatique, cet essai de phase II évalue le regorafenib après l'échec d'un traitement par imatinib ou sunitinib

    “Efficacy and Safety of Regorafenib in Patients With Metastatic and/or Unresectable GI Stromal Tumor After Failure of Imatinib and Sunitinib: A Multicenter Phase II Trial”

    • George, Suzanne;Wang, Qian;Heinrich, Michael C.;Corless, Christopher L.;Zhu, Meijun;Butrynski, James E.;Morgan, Jeffrey A.;Wagner, Andrew J.;Choy, Edwin;Tap, William D.;Yap, Jeffrey T.;Van den Abbeele, Annick D.;Manola, Judith B.;Solomon, Sarah M.;Fletcher, Jonathan A.;von Mehren, Margaret;Demetri, George D.

    Purpose Metastatic GI stromal tumor (GIST) is a life-threatening disease with no therapy of proven efficacy after failure of imatinib and sunitinib. Regorafenib is a structurally unique inhibitor of multiple cancer-associated kinases, including KIT and platelet-derived growth factor receptor (PDGFR), with broad-spectrum anticancer activity in preclinical and early-phase trials. Because KIT and PDGFR-α remain drivers of GIST after resistance to imatinib and sunitinib, we performed a multicenter single-stage phase II trial of regorafenib in patients with advanced GIST after failure of at least imatinib and sunitinib.Patients and Methods Patients received regorafenib orally, 160 mg daily, on days 1 to 21 of a 28-day cycle. Disease assessment was performed every two cycles per RECIST 1.1. Primary end point was clinical benefit rate (CBR), defined as objective responses (ie, complete or partial response [PR] as well as stable disease [SD] ≥ 16 weeks). Serial tumor biopsies were obtained ...


Mots clés : Appareil digestif (autre); Traitements (Traitements systémiques : applications cliniques)

Cet article passe en revue les recommandations relatives à la prise en charge des toxicités oculaires associées aux thérapies ciblées du cancer

  • Ocular Toxicity of Targeted Therapies
    Journal of Clinical Oncology, sous presse, 2012 (résumé)
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    Cet article passe en revue les recommandations relatives à la prise en charge des toxicités oculaires associées aux thérapies ciblées du cancer

    “Ocular Toxicity of Targeted Therapies”

    • Renouf, Daniel J.;Velazquez-Martin, Juan P.;Simpson, Rand;Siu, Lillian L.;Bedard, Philippe L.

    Molecularly targeted agents are commonly used in oncology practice, and many new targeted agents are currently being tested in clinical trials. Although these agents are thought to be more specific and less toxic then traditional cytotoxic chemotherapy, they are associated with a variety of toxicities, including ocular toxicity. Many of the molecules targeted by anticancer agents are also expressed in ocular tissues. We reviewed the literature for described ocular toxicities associated with both approved and investigational molecularly targeted agents. Ocular toxicity has been described with numerous approved targeted agents and also seems to be associated with several classes of agents currently being tested in early-phase clinical trials. We discuss the proposed pathogenesis, monitoring guidelines, and management recommendations. It is important for oncologists to be aware of the potential for ocular toxicity, with prompt recognition of symptoms that require referral to an ...


Mots clés : Cancer (général); Traitements (Traitements systémiques : applications cliniques)

Combinaison de traitements localisés et systémiques

Mené sur 826 patients pédiatriques atteints d'un lymphome hodgkinien, cet essai évalue, du point de vue de la survie sans événement et de la survie globale à 10 ans, l'intérêt d'une radiothérapie du champ impliqué en combinaison avec une chimiothérapie

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    Mené sur 826 patients pédiatriques atteints d'un lymphome hodgkinien, cet essai évalue, du point de vue de la survie sans événement et de la survie globale à 10 ans, l'intérêt d'une radiothérapie du champ impliqué en combinaison avec une chimiothérapie

    “Long-Term Results of CCG 5942: A Randomized Comparison of Chemotherapy With and Without Radiotherapy for Children With Hodgkin's Lymphoma—A Report From the Children's Oncology Group”

    • Wolden, Suzanne L.;Chen, Lu;Kelly, Kara M.;Herzog, Philip;Gilchrist, Gerald S.;Thomson, John;Sposto, Richard;Kadin, Marshall E.;Hutchinson, Raymond J.;Nachman, James

    Purpose In 1995, the Children's Cancer Group (CCG) opened a trial for patients with Hodgkin's lymphoma evaluating whether low-dose involved-field radiation therapy (IFRT) improved event-free survival (EFS) for patients achieving a complete response after chemotherapy. We present the long-term study outcome using final data through March 2007.Patients and Methods Between January 1995 and December 1998, 826 eligible patients were enrolled onto CCG 5942. Four hundred ninety-eight patients achieving an initial complete response to chemotherapy were randomly assigned to receive IFRT or no further therapy. EFS and overall survival (OS) were assessed from the date of study entry or random assignment, as appropriate.Results Ten-year EFS and OS rates for the entire cohort were 83.5% and 92.5%, respectively. In an as-treated analysis for randomly assigned patients, the 10-year EFS and OS rates were 91.2% and 97.1%, respectively, for IFRT and 82.9% and 95.9%, respectively, for no further ...


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

Mené sur 1 236 patients atteints d'un carcinome localement avancé du rectum, cet essai multicentrique allemand de phase III évalue la réponse complète et la toxicité associées à l'ajout d'oxaliplatine au fluorouracile dans la chimioradiothérapie pré-opératoire et la chimiothérapie post-opératoire

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    Mené sur 1 236 patients atteints d'un carcinome localement avancé du rectum, cet essai multicentrique allemand de phase III évalue la réponse complète et la toxicité associées à l'ajout d'oxaliplatine au fluorouracile dans la chimioradiothérapie pré-opératoire et la chimiothérapie post-opératoire

    “Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial”

    • Rödel, Claus;Liersch, Torsten;Becker, Heinz;Fietkau, Rainer;Hohenberger, Werner;Hothorn, Torsten;Graeven, Ullrich;Arnold, Dirk;Lang-Welzenbach, Marga;Raab, Hans-Rudolf;Sülberg, Heiko;Wittekind, Christian;Potapov, Sergej;Staib, Ludger;Hess, Clemens;Weigang-Köhler, Karin;Grabenbauer, Gerhard G.;Hoffmanns, Hans;Lindemann, Fritz;Schlenska-Lange, Anke;Folprecht, Gunnar;Sauer, Rolf

    Background : Preoperative chemoradiotherapy, total mesorectal excision surgery, and adjuvant chemotherapy with fluorouracil is the standard combined modality treatment for rectal cancer. With the aim of improving disease-free survival (DFS), this phase 3 study (CAO/ARO/AIO-04) integrated oxaliplatin into standard treatment. Methods : This was a multicentre, open-label, randomised, phase 3 study in patients with histologically proven carcinoma of the rectum with clinically staged T3–4 or any node-positive disease. Between July 25, 2006, and Feb 26, 2010, patients were randomly assigned to two groups: a control group receiving standard fluorouracil-based combined modality treatment, consisting of preoperative radiotherapy of 50·4 Gy plus infusional fluorouracil (1000 mg/m2 days 1–5 and 29–33), followed by surgery and four cycles of bolus fluorouracil (500 mg/m2 days 1–5 and 29; fluorouracil group); and an experimental group receiving preoperative radiotherapy of 50·4 Gy plus ...


  • Rectal cancer ? the times they are a-changing
    The Lancet Oncology, sous presse, 2012 (commentaire)
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    Mené sur 1 236 patients atteints d'un carcinome localement avancé du rectum, cet essai multicentrique allemand de phase III évalue la réponse complète et la toxicité associées à l'ajout d'oxaliplatine au fluorouracile dans la chimioradiothérapie pré-opératoire et la chimiothérapie post-opératoire

    “Rectal cancer ? the times they are a-changing”

    • Glynne-Jones, Robert


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

Ressources et infrastructures (Traitements)

Cet article propose des recommandations pour mener des essais cliniques de traitements néoadjuvants dans le cancer du sein

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    Cet article propose des recommandations pour mener des essais cliniques de traitements néoadjuvants dans le cancer du sein

    “A common language in neoadjuvant breast cancer clinical trials: proposals for standard definitions and endpoints”

    • Fumagalli, Debora;Bedard, Philippe L.;Nahleh, Zeina;Michiels, Stefan;Sotiriou, Christos;Loi, Sherene;Sparano, Joseph A.;Ellis, Matthew;Hylton, Nola;Zujewski, Jo Anne;Hudis, Clifford;Esserman, Laura;Piccart, Martine

    The neoadjuvant setting provides a unique opportunity to study the effect of systemic treatments on breast cancer biology and to identify clinically useful prognostic and predictive biomarkers. Discrepancies and inconsistencies in the use of definitions and endpoint assessments in this setting confound the analysis and interpretation of results across clinical trials and hinder research progress. This Review represents a joint effort of the Breast International Group and the National Cancer Institute-sponsored North American Breast Cancer Group to provide clinicians and researchers with a series of standardised definitions and endpoints that could be implemented in future neoadjuvant clinical trials. Definitions of the setting of interest and of survival endpoints are recommended, together with proposals for standard assessment of the response to treatment, use of functional and molecular imaging endpoints, and characterisation and selection of the population to treat. We expect that ...


Mots clés : Sein; Traitements (Ressources et infrastructures (Traitements))

A partir d'une revue systématique de la littérature en matière d'essais cliniques de nouveaux traitements du cancer du poumon, cette étude analyse les différences entre les conclusions des résumés et le corps des articles

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    A partir d'une revue systématique de la littérature en matière d'essais cliniques de nouveaux traitements du cancer du poumon, cette étude analyse les différences entre les conclusions des résumés et le corps des articles

    “Discordance Between Conclusions Stated in the Abstract and Conclusions in the Article: Analysis of Published Randomized Controlled Trials of Systemic Therapy in Lung Cancer”

    • Altwairgi, Abdullah K.;Booth, Christopher M.;Hopman, Wilma M.;Baetz, Tara D.

    Purpose Clinicians may read only the abstract of an article to keep abreast of newly published randomized controlled trials (RCTs). However, discordances have been noticed in summary conclusions in the abstracts and the main body of some articles. This article evaluated such discordances in detail.Methods RCTs of systemic therapy for lung cancer published between 2004 and 2009 were considered. Conclusions in the body of the articles and those in the abstracts were graded by using a 7-point Likert scale; 1 for strong endorsement of the control arm, 4 for a neutral statement, and 7 for strong endorsement of the experimental arm. Conclusions were classified as discordant if the difference in scores was ≥ 2. χ2 tests and logistic regression were used to identify factors associated with discordance.Results From among 114 eligible RCTs identified (90 for non–small-cell and 24 for small-cell lung cancer), 11 (10%) articles presented discordant conclusions in the abstract and in the body ...


Mots clés : Poumon; Traitements (Ressources et infrastructures (Traitements))

Cet article propose dix recommandations pour combler le déficit de crédibilité imputé aux recherches cliniques financées par l'industrie pharmaceutique

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    Cet article propose dix recommandations pour combler le déficit de crédibilité imputé aux recherches cliniques financées par l'industrie pharmaceutique

    “Ten Recommendations for Closing the Credibility Gap in Reporting Industry-Sponsored Clinical Research: A Joint Journal and Pharmaceutical Industry Perspective”

    • Mansi, Bernadette A.;Clark, Juli;David, Frank S.;Gesell, Thomas M.;Glasser, Susan;Gonzalez, John;Haller, Daniel G.;Laine, Christine;Miller, Charles L.;Mooney, LaVerne A.;Zecevic, Maja

    The credibility of industry-sponsored clinical research has suffered in recent years, undercut by reports of selective or biased disclosure of research results, ghostwriting and guest authorship, and inaccurate or incomplete reporting of potential conflicts of interest. [1] and [2] In response, many pharmaceutical companies have integrated best practices and recommendations from groups such as the International Committee of Medical Journal Editors (ICMJE), the Good Publication Practice guidelines, the Committee on Publication Ethics, the EQUATOR (Enhancing the QUAlity and Transparency Of health Resources) Network, and the Medical Publishing Insights and Practices (MPIP) initiative into their internal policies and standard operating procedures. [3], [4], [5], [6], [7], [8], [9] and [10] However, a credibility gap remains: some observers, including some journal editors and academic reviewers, maintain a persistent negative view of industry-sponsored studies.11 Given industry's pivotal ...


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

Cet article passe en revue les différentes approches susceptibles d'être menées dans un cadre translationnel pour évaluer et traiter les effets indésirables induits par les traitements du cancer

  • Translational approaches to treatment-induced symptoms in cancer patients
    Nature Reviews Clinical Oncology, sous presse, 2012 (résumé)
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    Cet article passe en revue les différentes approches susceptibles d'être menées dans un cadre translationnel pour évaluer et traiter les effets indésirables induits par les traitements du cancer

    “Translational approaches to treatment-induced symptoms in cancer patients”

    • Dantzer, Robert;Meagher, Mary W.;Cleeland, Charles S.

    Cancer therapy makes patients sick. The therapies that are available to clinicians allow them to successfully control nausea, emesis and pain. However, this is not the case for a number of other symptoms that include fatigue, distractibility, poor memory, and diminished interest in previously pleasurable activities. These symptoms cluster during the course of cancer therapy and impair patient quality of life, limit therapy options and do not always resolve at the cessation of treatment. It is possible to describe the intensity and temporal features of symptoms and assess their relationship with the inflammatory response that is associated with cancer and cancer therapy. At the preclinical level, sophisticated animal models still need to be deployed to study the causal role of inflammation in specific components of cancer-related symptoms. Various approaches can be optimally combined in a translational symptom research pathway to provide a framework for assessing in a systematic manner ...


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

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