Menée à l'aide d'un modèle murin, cette étude met en évidence l'intérêt des champs électriques pulsés d'une durée de 100 nanosecondes pour traiter un carcinome hépatocellulaire et réduire le risque de récidive

A protective effect after clearance of orthotopic rat hepatocellular carcinoma by nanosecond pulsed electric fields

Chen, Ru ; Sain, Nova M. ; Harlow, K. Tyler ; Chen, Yeong-Jer ; Shires, Peter K. ; Heller, Richard ; Beebe, Stephen J.

Strategies for treating liver cancer using radiation, chemotherapy combinations and tyrosine kinase inhibitors targeting specific mutations have provided longer survival times, yet multiple treatments are often needed and recurrences with new malignant phenotypes are not uncommon. New and innovative treatments are undoubtedly needed to successfully treat liver cancer. Over the last decade, nanosecond pulsed electric fields (nsPEFs) have shown promise in pre-clinical studies; however, these have [...]

Cet article fait le point sur les complications associées à une radiothérapie de la région pelvienne chez les patientes atteintes d'un cancer gynécologique

Complications of pelvic radiation in patients treated for gynecologic malignancies

Viswanathan, Akila N. ; Lee, Larissa J. ; Eswara, Jairam R. ; Horowitz, Neil S. ; Konstantinopoulos, Panagiotis A. ; Mirabeau-Beale, Kristina L. ; Rose, Brent S. ; Keudell, Arvind G. von ; Wo, Jennifer Y.

Radiation therapy is a critical treatment modality in the management of patients with gynecologic tumors. New highly conformal external-beam and brachytherapy techniques have led to important reductions in recurrence and patient morbidity and mortality. However, patients who receive pelvic radiation for gynecologic malignancies may experience a unique constellation of toxicity because of the anatomic locations, combination with concurrent chemotherapy and/or surgery, as well as potential [...]

Menée sur 107 patients atteints d'un cancer localement avancé avec envahissement vasculaire et traités entre mai 2010 et janvier 2012, cette étude évalue, du point de vue de la survie sans récidive locale et des événements indésirables, l'intérêt d'un traitement ablatif par électroporation irréversible

Irreversible electroporation of unresectable soft tissue tumors with vascular invasion: effective palliation

Martin, Robert ; Philips, Prejesh ; Ellis, Susan ; Hayes, David ; Bagla, Sandeep

Background : Irreversible electroporation (IRE) has recently been added as an additional therapeutic ablative option in patients with locally advanced cancers (LAC) involving vital structures. IRE delivers localized electric current by peri-tumoral discrete probes to attain irreversible changes in cell membrane leading to cell death. The aim of this study was to evaluate the long-term effects of IRE in the treatment of locally advanced tumors. Methods : A prospective IRB approved evaluation of [...]

Mené sur 80 patients atteints d'un cancer du poumon non à petites cellules de stade T1-3 N0 M0 (âge médian : 75,9 ans ; durée médiane de suivi : 49 mois), cet essai multicentrique de phase II évalue l'efficacité, du point de vue des taux actuariels de récidive régionale ou de récidive à distance et du taux de survie globale à 2 ans, ainsi que la toxicité d'une radiothérapie conformationnelle 3D, accélérée et hypofractionnée

Phase II Study of Accelerated Hypofractionated Three-Dimensional Conformal Radiotherapy for Stage T1-3 N0 M0 Non–Small Cell Lung Cancer: NCIC CTG BR.25

Cheung, Patrick ; Faria, Sergio ; Ahmed, Shahida ; Chabot, Pierre ; Greenland, Jonathan ; Kurien, Elizabeth ; Mohamed, Islam ; Wright, James R. ; Hollenhorst, Helmut ; de Metz, Catherine ; Campbell, Holly ; Vu, Thi Toni ; Karvat, Anand ; Wai, Elaine S. ; Ung, Yee C. ; Goss, Glenwood ; Shepherd, Frances A. ; O’Brien, Patti ; Ding, Keyue ; O’Callaghan, Chris

Background : A multi-institutional phase II trial was performed to assess a hypofractionated accelerated radiotherapy regimen for early stage non–small cell lung cancer (NSCLC) in an era when stereotactic body radiotherapy was not widely available. Methods : Eighty patients with biopsy-proven, peripherally located, T1-3 N0 M0 NSCLC were enrolled. Eligible patients received 60 Gy in 15 fractions using a three-dimensional conformal technique without inhomogeneity correction. The gross tumour [...]

A partir d'une revue systématique de la littérature publiée jusqu'en décembre 2013 (23 études, 19 793 patients), cette étude évalue le bénéfice, en termes de survie, d'une lymphadénectomie étendue chez les patients atteints d'un cancer invasif de la vessie traité par cystectomie radicale

The Impact of the Extent of Lymphadenectomy on Oncologic Outcomes in Patients Undergoing Radical Cystectomy for Bladder Cancer: A Systematic Review

Bruins, Harman M. ; Veskimae, Erik ; Hernandez, Virginia ; Imamura, Mari ; Neuberger, Molly M. ; Dahm, Philip ; Stewart, Fiona ; Lam, Thomas B. ; N’Dow, James ; van der Heijden, Antoine G. ; Compérat, Eva ; Cowan, Nigel C. ; De Santis, Maria ; Gakis, Georgios ; Lebret, Thierry ; Ribal, Maria J. ; Sherif, Amir ; Witjes, J. Alfred

Context : Controversy exists regarding the therapeutic value of lymphadenectomy (LND) in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). Objective : To systematically review the relevant literature assessing the impact of LND on oncologic and perioperative outcomes in patients undergoing RC for MIBC. Evidence acquisition : Medline, Medline In-Process, Embase, the Cochrane Central Register of Controlled Trials, and the Latin American and Caribbean Center on [...]

Mené sur 117 patients atteints d'un carcinome rhinopharyngé non métastatique ayant récidivé localement et traités entre 2003 et 2007 (durée médiane de suivi : 25 mois), cet essai de phase II évalue l'efficacité, du point de vue de la survie globale à 5 ans, et les complications à long terme de deux protocoles de radiothérapie avec modulation d'intensité : l'un délivrant une dose totale de rayonnements de 60 gray en 27 fractions et l'autre 68 gray en 34 fractions

Effect of total dose and fraction size on survival of patients with locally recurrent nasopharyngeal carcinoma treated with intensity-modulated radiotherapy: A phase 2, single-center, randomized controlled trial

Tian, Yun-ming ; Zhao, Chong ; Guo, Ying ; Huang, Ying ; Huang, Shao-Min ; Deng, Xiao-Wu ; Lin, Cheng-Guang ; Lu, Tai-Xiang ; Han, Fei

BACKGROUND : The optimal model of total dose and fraction size for patients with locally recurrent nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) remains unclear. The authors designed a randomized phase 2 clinical trial to investigate the efficacy of 2 different models, with the objective of determining an optimal model. METHODS : Between January 2003 and December 2007, a total of 117 patients with locally recurrent nonmetastatic nasopharyngeal carcinoma were [...]

Menée à partir de données portant sur 131 patients atteints d'un paragangliome bénin de la tête et du cou traité entre 1968 et 2011 (durée médiane de suivi : 8,7 ans), cette étude évalue, du point de vue des taux de contrôle local de la maladie et des taux de survie à 5 et 10 ans, l'efficacité d'une radiothérapie

Radiotherapy for benign head and neck paragangliomas: A 45-year experience

Gilbo, Philip ; Morris, Christopher G. ; Amdur, Robert J. ; Werning, John W. ; Dziegielewski, Peter T. ; Kirwan, Jessica ; Mendenhall, William M.

BACKGROUND : Paragangliomas of the head and neck are rare, slow-growing, generally benign tumors of neuroendocrine cells associated with the peripheral nervous system that commonly involve the carotid body, jugular bulb, vagal ganglia, and temporal bone. Treatment options include surgery, radiotherapy (RT), stereotactic radiosurgery (SRS), and observation. This article briefly reviews our 45-year institutional experience treating this neoplasm with RT. METHODS : From January 1968 through March [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, dans les cellules endothéliales, l'expression de la kinase d'adhérence focale FAK régule la sensibilité des tumeurs à la doxorubicine

Endothelial-cell FAK targeting sensitizes tumours to DNA-damaging therapy

Tavora, Bernardo ; Reynolds, Louise E. ; Batista, Silvia ; Demircioglu, Fevzi ; Fernandez, Isabelle ; Lechertier, Tanguy ; Lees, Delphine M. ; Wong, Ping-Pui ; Alexopoulou, Annika ; Elia, George ; Clear, Andrew ; Ledoux, Adeline ; Hunter, Jill ; Perkins, Neil ; Gribben, John G. ; Hodivala-Dilke, Kairbaan M.

Chemoresistance is a serious limitation of cancer treatment. Until recently, almost all the work done to study this limitation has been restricted to tumour cells. Here we identify a novel molecular mechanism by which endothelial cells regulate chemosensitivity. We establish that specific targeting of focal adhesion kinase (FAK; also known as PTK2) in endothelial cells is sufficient to induce tumour-cell sensitization to DNA-damaging therapies and thus inhibit tumour growth in mice. The [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude met en évidence des mécanismes par lesquels, dans les cellules tumorales exposées à une thérapie ciblée, l'activation de Stat3 favorise la résistance thérapeutique

Drug Resistance via Feedback Activation of Stat3 in Oncogene-Addicted Cancer Cells

Lee, Ho-June ; Zhuang, Guanglei ; Cao, Yi ; Du, Pan ; Kim, Hyo-Jin ; Settleman, Jeff

Pathway-targeted cancer drugs can produce dramatic responses that are invariably limited by the emergence of drug-resistant cells. We found that many drug-treated "oncogene-addicted" cancer cells engage a positive feedback loop leading to Stat3 activation, consequently promoting cell survival and limiting overall drug response. This was observed in cancer cells driven by diverse activated kinases, including EGFR, HER2, ALK, and MET, as well as mutant KRAS. Specifically, MEK inhibition led to [...]

Cet article passe en revue les travaux récents sur les mécanismes de résistance aux immunothérapies des cancers

Acquired and intrinsic resistance in cancer immunotherapy

Kelderman, Sander ; Schumacher, Ton N. M. ; Haanen, John B. A. G.

A number of immunotherapies, in particular immune checkpoint targeting antibodies and adoptive T-cell therapies, are starting to transform the treatment of advanced cancers. The likelihood to respond to these immunotherapies differs strongly across tumor types, with response rates for checkpoint targeting being the highest in advanced melanoma, renal cell cancer and non-small cell lung cancer. However, also non-responsiveness is observed, indicating the presence of intrinsic resistance or [...]

Menée in vitro et in vivo, cette étude évalue l'activité antitumorale d'un composé appelé TTT-3002, un inhibiteur de FLT3, pour le traitement d'une leucémie myéloïde aiguë

FLT3 kinase inhibitor TTT-3002 overcomes both activating and drug resistance mutations in FLT3 in acute myeloid leukemia

Ma, Hayley S. ; Nguyen, Bao ; Duffield, Amy S. ; Li, Li ; Galanis, Allison ; Williams, Allen B. ; Brown, Patrick A ; Levis, Mark J ; Leahy, Daniel J. ; Small, Donald

There have been a number of clinical trials testing the efficacy of FLT3 tyrosine kinase inhibitors (TKIs) in acute myeloid leukemia (AML) patients harboring a constitutively activating mutation in FLT3. However, there has been limited efficacy, most often due to inadequate achievement of FLT3 inhibition through a variety of mechanisms. In a previous study, TTT-3002 was identified as a novel FLT3 inhibitor with the most potent activity to date against FLT3 internal tandem duplication (FLT3/ITD) [...]

Menée in vitro et in vivo, cette étude suggère l'intérêt de combiner un inhibiteur de MYC et un inhibiteur de β-caténine pour le traitement des lymphomes liés à une surexpression de MYC

Addiction to multiple oncogenes can be exploited to prevent the emergence of therapeutic resistance

Choi, Peter S. ; Li, Yulin ; Felsher, Dean W.

Many cancers exhibit sensitivity to the inhibition of a single genetic lesion, a property that has been successfully exploited with oncogene-targeted therapeutics. However, inhibition of single oncogenes often fails to result in sustained tumor regression due to the emergence of therapy-resistant cells. Here, we report that MYC-driven lymphomas frequently acquire activating mutations in β-catenin, including a previously unreported mutation in a splice acceptor site. Tumors with these genetic [...]

Cet article passe en revue les travaux récents sur le développement de nouveaux traitements pour les patients atteints d'un mélanome métastatique présentant un gène BRAF muté

Systemic treatment for BRAF-mutant melanoma: where do we go next?

Menzies, Alexander M. ; Long, Georgina V.

After decades of treatment failure for metastatic melanoma, the development of BRAF inhibitors was highly anticipated to dramatically improve outcomes for patients with oncogene-addictedBRAF-mutant metastatic melanoma. Rapid and frequent responses occurred with BRAF inhibitors, but clinical benefit was usually transient because of the rapid emergence of drug resistance. Concurrently, and by contrast, ipilimumab, a novel immune checkpoint inhibitor, was shown to provide long-term clinical [...]

Menée sur des lignées cellulaires, à l'aide de xénogreffes et d'échantillons tumoraux prélevés sur des patients atteints d'un mélanome métastatique, cette étude met en évidence des mécanismes par lesquels le complexe elF4F favorise l'apparition d'une résistance à une thérapie ciblée anti BRAF et/ou MEK dans le traitement d'un mélanome présentant la mutation V600E du gène BRAF

eIF4F is a nexus of resistance to anti-BRAF and anti-MEK cancer therapies

Boussemart, Lise ; Malka-Mahieu, Helene ; Girault, Isabelle ; Allard, Delphine ; Hemmingsson, Oskar ; Tomasic, Gorana ; Thomas, Marina ; Basmadjian, Christine ; Ribeiro, Nigel ; Thuaud, Frederic ; Mateus, Christina ; Routier, Emilie ; Kamsu-Kom, Nyam ; Agoussi, Sandrine ; Eggermont, Alexander M. ; Desaubry, Laurent ; Robert, Caroline ; Vagner, Stephan

In BRAF(V600)-mutant tumours, most mechanisms of resistance to drugs that target the BRAF and/or MEK kinases rely on reactivation of the RAS–RAF–MEK–ERK mitogen-activated protein kinase (MAPK) signal transduction pathway, on activation of the alternative, PI(3)K–AKT–mTOR, pathway (which is ERK independent) or on modulation of the caspase-dependent apoptotic cascade. All three pathways converge to regulate the formation of the eIF4F eukaryotic translation initiation complex, which binds to the [...]

Menée in vitro et in vivo, cette étude suggère l'intérêt d'un composé appelé POL6926, un inhibiteur de CXCR7, pour le traitement des patients atteints d'un myélome multiple

CXCR7-dependent angiogenic mononuclear cells trafficking regulates tumor progression in multiple myeloma

Azab, Abdel Kareem ; Sahin, Ilyas ; Azab, Feda ; Moschetta, Michele ; Mishima, Yuji ; Burwick, Nicholas ; Zimmermann, Johann ; Romagnoli, Barbara ; Patel, Kalpana ; Chevalier, Eric ; Roccaro, Aldo M. ; Ghobrial, Irene M.

Angiogenesis is a hallmark of progression in multiple myeloma (MM), and many studies have shown that angiogenesis should be considered as a therapeutic target in MM. The CXCR4/SDF-1 axis is essential for cell trafficking and has been shown to regulate tumor progression and metastasis in many tumors including MM. A second chemokine receptor for SDF-1, CXCR7 was discovered recently and is expressed on activated endothelial cells. In this study, we examined the role of CXCR7 in angiogenic [...]

Cet article passe en revue les perspectives offertes par les connaissances sur le micro-environnement tumoral pour le développement de nouveaux traitements, y compris en immunothérapie, des cancers du poumon non à petites cellules

Non-small-cell lung cancers: a heterogeneous set of diseases

Chen, Zhao ; Fillmore, Christine M. ; Hammerman, Peter S. ; Kim, Carla F. ; Wong, Kwok-Kin

Non-small-cell lung cancers (NSCLCs), the most common lung cancers, are known to have diverse pathological features. During the past decade, in-depth analyses of lung cancer genomes and signalling pathways have further defined NSCLCs as a group of distinct diseases with genetic and cellular heterogeneity. Consequently, an impressive list of potential therapeutic targets was unveiled, drastically altering the clinical evaluation and treatment of patients. Many targeted therapies have been [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude suggère l'intérêt d'un composé appelé ISA-2011B, un inhibteur de la kinase PIP5K1α, pour le traitement des patients atteints d'un cancer de la prostate de stade avancé

The role of PI3K/AKT-related PIP5K1alpha and the discovery of its selective inhibitor for treatment of advanced prostate cancer

Semenas, Julius ; Hedblom, Andreas ; Miftakhova, Regina R. ; Sarwar, Martuza ; Larsson, Rikard ; Shcherbina, Liliya ; Johansson, Martin E. ; Härkönen, Pirkko ; Sterner, Olov ; Persson, Jenny L.

Nitrogen-containing heterocyclic compounds are an important class of molecules that are commonly used for the synthesis of candidate drugs. Phosphatidylinositol-4-phosphate 5-kinase-α (PIP5Kα) is a lipid kinase, similar to PI3K. However, the role of PIP5K1α in oncogenic processes and the development of inhibitors that selectively target PIP5K1α have not been reported. In the present study we report that overexpression of PIP5K1α is associated with poor prognosis in prostate cancer and [...]

Menée à l'aide de xénogreffes de tumeurs mammaires sur des rats, cette étude met en évidence des mécanismes par lesquels, en réduisant la production de mélatonine, une exposition nocturne à la lumière favorise la résistance au tamoxifène

Circadian and Melatonin Disruption by Exposure to Light at Night Drives Intrinsic Resistance to Tamoxifen Therapy in Breast Cancer

Dauchy, Robert T. ; Xiang, Shulin ; Mao, Lulu ; Brimer, Samantha ; Wren, Melissa A. ; Yuan, Lin ; Anbalagan, Muralidharan ; Hauch, Adam ; Frasch, Tripp ; Rowan, Brian G. ; Blask, David E. ; Hill, Steven M.

Resistance to endocrine therapy is a major impediment to successful treatment of breast cancer. Preclinical and clinical evidence links resistance to antiestrogen drugs in breast cancer cells with the overexpression and/or activation of various pro-oncogenic tyrosine kinases. Disruption of circadian rhythms by night shift work or disturbed sleep-wake cycles may lead to an increased risk of breast cancer and other diseases. Moreover, light exposure at night (LEN) suppresses the nocturnal [...]

Mené sur 44 patients atteints d'une tumeur stromale gastro-intestinale de stade avancé après l'échec d'un traitement par imatinib, cet essai randomisé compare l'efficacité, du point de vue de la survie sans progression, et la toxicité du masitinib par rapport au sunitinib (durée médiane de suivi : 14 mois)

Masitinib in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib: A randomized controlled open-label trial

Adenis, A. ; Blay, J.-Y. ; Bui-Nguyen, B. ; Bouché, O. ; Bertucci, F. ; Isambert, N. ; Bompas, E. ; Chaigneau, L. ; Domont, J. ; Ray-Coquard, I. ; Blésius, A. ; Van Tine, B. A. ; Bulusu, V. R. ; Dubreuil, P. ; Mansfield, C. D. ; Acin, Y. ; Moussy, A. ; Hermine, O. ; Le Cesne, A.

Background : Masitinib is a highly selective tyrosine kinase inhibitor with activity against the main oncogenic drivers of gastrointestinal stromal tumor (GIST). Masitinib was evaluated in patients with advanced GIST after imatinib failure or intolerance. Patients and methods : Prospective, multicenter, randomized, open-label trial. Patients with inoperable, advanced imatinib-resistant GIST were randomized (1 : 1) to receive masitinib (12 mg/kg/day) or sunitinib (50 mg/day [...]

Mené sur 73 patients atteints d'un cancer hématologique de stade avancé, notamment d'un myélome multiple, cet essai de phase I évalue la dose maximale recommandée et l'activité clinique de l'afuresertib, un inhibiteur de AKT par voie orale

Novel AKT inhibitor afuresertib shows favorable safety, pharmacokinetics, and clinical activity in multiple myeloma: Phase 1 study results

Spencer, Andrew ; Yoon, Sung-Soo ; Harrison, Simon J. ; Morris, Shannon R. ; Smith, Deborah A. ; Brigandi, Richard A. ; Gauvin, Jennifer ; Kumar, Rakesh ; Opalinska, Joanna B. ; Chen, Christine

The PI3K/AKT pathway is constitutively active in multiple cancers, including hematologic malignancies, providing proliferative and anti-apoptotic signals and possibly contributing to drug resistance. We conducted an open-label phase 1 study to evaluate the maximum tolerated dose (MTD), safety, pharmacokinetics, and clinical activity of afuresertib—an oral AKT inhibitor—in patients with advanced hematologic malignancies. Seventy-three patients (median age: 63 years) were treated at doses ranging [...]

Mené sur 107 patientes atteintes d'un cancer de l'ovaire, de la trompe de Fallope ou du péritoine résistant aux sels de platines (âge médian : 63 ans), cet essai randomisé évalue l'efficacité, du point de vue du taux de survie sans progression à 6 mois, et la toxicité de l'ajout de saracatinib au paclitaxel

A randomised placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer

McNeish, I.A. ; Ledermann, J.A. ; Webber, L. ; James, L. ; Kaye, S.B. ; Hall, M. ; Hall, G. ; Clamp, A. ; Earl, H. ; Banerjee, S. ; Kristeleit, R. ; Raja, F. ; Feeney, A. ; Lawrence, C. ; Dawson-Athey, L. ; Persic, M. ; Khan, I.

Background : We investigated whether the Src inhibitor saracatinib (AZD0530) improved efficacy of weekly paclitaxel in platinum-resistant ovarian cancer. Patients and Methods : Patients with platinum-resistant ovarian, fallopian tube or primary peritoneal cancer were randomised 2:1 to receive eight-week cycles of weekly paclitaxel (wPxl; 80 mg/m2/week x6 with 2 week break) plus saracatinib (S; 175 mg od) or placebo (P) continuously, starting 1 week prior to wPxl, until disease progression. [...]

Mené sur 327 patients atteints d'un adénocarcinome avancé du poumon sans mutation du gène KRAS, cet essai évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'erlotinib en traitement de deuxième ou troisième ligne

Effectiveness of erlotinib treatment in advanced KRAS mutation-negative lung adenocarcinoma patients: results of a multicenter observational cohort study (MOTIVATE)

Sarosi, Veronika ; Losonczy, Gyorgy ; Francovszky, Eva ; Tolnay, Edina ; Torok, Szilvia ; Galffy, Gabriella ; Hegedus, Balazs ; Döme, Balazs ; Ostoros, Gyula

Objectives : Erlotinib is an epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI), used for the treatment of non-small cell lung cancer. As the clinical significance of KRAS mutational status has not yet been clearly determined in this setting, our aim was to investigate the efficacy of erlotinib in advanced KRAS mutation-negative lung adenocarcinoma patients. Materials and methods : MOTIVATE is an open-label, multicenter, observational trial with Tarceva® (erlotinib) [...]

Cet article passe en revue les travaux récents sur les combinaisons de traitements susceptibles d'être mis en œuvre pour surmonter l'apparition d'une résistance au trastuzumab chez les patientes atteintes d'un cancer du sein HER2+ métastatique

Personalized drug combinations to overcome trastuzumab resistance in HER2-positive breast cancer

Vu, Thuy ; Sliwkowski, Mark X. ; Claret, Francois X.

HER2-positive (HER2 +) breast cancer accounts for 18%–20% of all breast cancer cases and has the second poorest prognosis among breast cancer subtypes. Trastuzumab, the first Food and Drug Administration-approved targeted therapy for breast cancer, established the era of personalized treatment for HER2 + metastatic disease. It is well tolerated and improves overall survival and time-to-disease progression; with chemotherapy, it is part of the standard of care for patients with HER2 + metastatic [...]

Mené sur 9 patientes atteintes d'un cancer du sein HER2-, cet essai de phase I évalue la dose maximale recommandée du nintedanib en complément d'une chimiothérapie de référence

Phase I clinical trial of nintedanib plus paclitaxel in early HER-2-negative breast cancer (CNIO-BR-01-2010/GEICAM-2010-10 study)

Quintela-Fandino, M. ; Urruticoechea, A. ; Guerra, J. ; Gil, M. ; Gonzalez-Martin, A. ; Marquez, R. ; Hernandez-Agudo, E. ; Rodriguez-Martin, C. ; Gil-Martin, M. ; Bratos, R. ; Escudero, M. J. ; Vlassak, S. ; Hilberg, F. ; Colomer, R.

Introduction: Previous small-molecule antiangiogenics have compromised chemotherapy dose intensity in breast cancer. We present a phase I trial of a novel selective agent, nintedanib, plus standard chemotherapy in early breast cancer. Methods: Her-2-negative breast cancer patients with tumours larger than 2 cm were eligible for dose-escalation trial (classic 3+3 method). Results: The recommended phase II dose (RP2D) was 150 mg BID of nintedanib combined with standard dose of weekly paclitaxel [...]

Mené sur 55 patientes atteintes d'un carcinome récidivant, persistant ou avancé du col de l'utérus, cet essai de phase II évalue l'effiacité, du point de vue du taux de réponse tumorale, et la toxicité du pemetrexed en combinaison avec du cisplatine

Pemetrexed and Cisplatin for the Treatment of Advanced, Persistent, or Recurrent Carcinoma of the Cervix: A Limited Access Phase II Trial of the Gynecologic Oncology Group

Miller, David Scott ; Blessing, John A. ; Ramondetta, Lois M. ; Pham, Huyen Q. ; Tewari, Krishnansu S. ; Landrum, Lisa M. ; Brown, Jubilee ; Mannel, Robert S.

Purpose : To estimate the antitumor activity of pemetrexed and cisplatin with objective tumor response (partial and complete) in patients with advanced, persistent, or recurrent carcinoma of the cervix and to determine the nature and degree of toxicity of this regimen. Secondarily, this study will determine the effects of this regimen on progression-free survival and overall survival. Patients and Methods : Eligible, consenting patients received pemetrexed 500 mg/m2 and cisplatin 50 mg/m2 [...]

Cet article passe en revue les stratégies thérapeutiques pour traiter un mélanome de la vulve, du vagin, de l'ovaire ou du col de l'utérus

Management of melanomas of the gynaecological tract

Nobbenhuis, Marielle A.E. ; Lalondrelle, Susan ; Larkin, James ; Banerjee, Susana

Purpose of review : Primary melanomas originating from the gynaecological tract are rare and aggressive cancers. The 5-year survival is around 10%. The majority of tumours differ from cutaneous melanomas, which arise from the skin, by developing from melanocytes located in mucosal epithelium. The clinical behaviour, prognosis and the biology of mucosal melanomas are distinct from cutaneous melanomas. In this article, we summarize the current management of melanomas of the gynaecological tract [...]

Menée sur un modèle murin de lymphome sous-cutané, cette étude évalue l'intérêt de réguler l'immunité antitumorale dépendante du complément pour améliorer l'efficacité de la radiothérapie

Complement-Dependent Modulation of Antitumor Immunity following Radiation Therapy

Elvington, Michelle ; Scheiber, Melissa ; Yang, Xiaofeng ; Lyons, Katherine ; Jacqmin, Dustin ; Wadsworth, Casey ; Marshall, David ; Vanek, Kenneth ; Tomlinson, Stephen

Complement is traditionally thought of as a proinflammatory effector mechanism of antitumor immunity. However, complement is also important for effective clearance of apoptotic cells, which can be an anti-inflammatory and tolerogenic process. We show that localized fractionated radiation therapy (RT) of subcutaneous murine lymphoma results in tumor cell apoptosis and local complement activation. Cotreatment of mice with tumor-targeted complement inhibition markedly improved therapeutic outcome [...]

Cet article présente les recommandations d'une société savante européenne sur le diagnostic d'un lymphome hodgkinien, la prise en charge thérapeutique des patients et leur suivi

Hodgkin's lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Eichenauer, D. A. ; Engert, A. ; André, M. ; Federico, M. ; Illidge, T. ; Hutchings, M. ; Ladetto, M.

incidence : The crude incidence of Hodgkin's lymphoma (HL) in the European Union is 2.3 and the mortality is 0.4 cases/100 000/year. Young adults aged 20–40 years are most often affected; however, a second incidence peak is seen in individuals aged 55 and older. Slightly more men than women are diagnosed with HL. Histologically, classical HL (cHL) accounting for ∼95% of all HL cases is distinguished from nodular lymphocyte-predominant HL (NLPHL) representing ∼5% of all HL cases. diagnosis : [...]

Menée sur 30 patients atteints d'une mélanome avec métastases cérébrales, cette étude met en évidence la faisabilité d'un traitement combinant une radiochirurgie stéréotaxique par Gamma Knife et un inhibiteur de BRAF

On demand Gamma-knife strategy can be safely combined with BRAF-inhibitors for the treatment of melanoma brain metastases

Gaudy-Marqueste, C. ; Carron, R. ; Delsanti, C. ; Loundou, A. ; Monestier, S. ; Archier, E. ; Richard, M.A. ; Regis, J. ; Grob, J.J.

Background : Both Gamma-Knife radiosurgery (GKRS) and BRAF-inhibitors (BRAF-I) have been shown to be useful in melanoma patients with brain metastases (BM), thus suggesting that it could be interesting to combine their respective advantages. However cases of radiosensitization following conventional radiation therapy in BRAF-I treated patients have raised serious concerns about the real feasibility and risk/benefit ratio of this combination. Patients and methods : review by 2 independent [...]

Cet article passe en revue les enjeux actuels du diagnostic et des traitements d'un mésothéliome pleural malin

Current Issues in Malignant Pleural Mesothelioma Evaluation and Management

Ai, Jing ; Stevenson, James P.

Malignant pleural mesothelioma (MPM) is an uncommon disease most often associated with occupational asbestos exposure and is steadily increasing in worldwide incidence. Patients typically present at an older age, with advanced clinical stage and other medical comorbidities, making management quite challenging. Despite great efforts, the prognosis of MPM remains poor, especially at progression after initial treatment. Macroscopic complete resection of MPM can be achieved through extrapleural [...]

Menée sur 80 patients atteints d'un cancer du poumon non à petites cellules avec plusieurs métastases cérébrales, cette étude évalue, du point de vue de la survie sans progression neurologique à 2 mois et de la survie globale, l'intérêt d'un protocole thérapeutique comportant un traitement par erlotinib, une radiothérapie concomitante du cerveau entier, puis un traitement d'entretien par erlotinib

Randomized Trial of Erlotinib Plus Whole-Brain Radiotherapy for NSCLC Patients With Multiple Brain Metastases

Lee, Siow Ming ; Lewanski, Conrad R. ; Counsell, Nicholas ; Ottensmeier, Christian ; Bates, Andrew ; Patel, Nirali ; Wadsworth, Christina ; Ngai, Yenting ; Hackshaw, Allan ; Faivre-Finn, Corinne

Background : Median survival of non-small cell lung cancer (NSCLC) patients with brain metastases is poor. We examined concurrent erlotinib and whole brain radiotherapy (WBRT) followed by maintenance erlotinib in patients with untreated brain metastases, given the potential radiosensitizing properties of erlotinib and its direct effect on brain metastases and systemic activity. Methods : Eighty NSCLC patients with KPS of 70 and greater and multiple brain metastases were randomly assigned to [...]

Cet article passe en revue les stratégies thérapeutiques pour traiter un cancer du poumon non à petites cellules chez les personnes âgées

A review of the management of elderly patients with non–small-cell lung cancer

Blanco, R. ; Maestu, I. ; de la Torre, M. G. ; Cassinello, A. ; Nuñez, I.

Most patients with non–small-cell lung cancer (NSCLC) are elderly but evidence to guide appropriate treatment decisions for this age group is generally scant. Careful evaluation of the elderly should be undertaken to ensure that treatment appropriate for the stage of the tumour is guided by patient characteristics and not by age. The Comprehensive Geriatric Assessment (CGA) remains the preferred option, but briefer tools may be appropriate to select patients for further evaluation. The [...]

Menée sur des modèles murins de cancer colorectal, cette étude montre que l'inhibition du facteur de croissance TGF bêta augmente l'efficacité d'une radiothérapie hypofractionnée

TGFβ inhibition prior to hypofractionated radiation enhances efficacy in preclinical models

Young, Kristina H ; Newell, Pippa ; Cottam, Benjamin ; Friedman, David ; Savage, Talicia ; Baird, Jason ; Akporiaye, Emmanuel ; Gough, Michael J ; Crittenden, Marka R

The immune infiltrate in colorectal cancer has been correlated with outcome, such that individuals with higher infiltrations of T cells have increased survival independent of disease stage. For those patients with poor immune infiltrates, overall survival is severely limited. Since the colorectal cancer patients studied received conventional cancer therapies, these data could be interpreted to mean that the pre-treatment tumor environment increases the efficacy of treatments such as [...]

Cet article analyse les conséquences inattendues de l'inflation du coût des thérapies ciblées du cancer

Unintended consequences of expensive cancer therapeutics—the pursuit of marginal indications and a me-too mentality that stifles innovation and creativity: The John Conley lecture

Fojo, T. ; Mailankody, S. ; Lo, A.

Cancer is expected to continue as a major health and economic problem worldwide. Several factors are contributing to the increasing economic burden imposed by cancer, with the cost of cancer drugs an undeniably important variable. The use of expensive therapies with marginal benefits for their approved indications and for unproven indications is contributing to the rising cost of cancer care. We believe that expensive therapies are stifling progress by (1) encouraging enormous expenditures of [...]

Cet article passe en revue les modèles murins pertinents et les méthodes d'obtention d'une leucémie myéloïde radio-induite dans le cadre de la recherche de traitements contre les cancers secondaires associés aux rayonnements ionisants

Radiation-induced myeloid leukemia in murine models

Rivina, Leena ; Davoren, Michael ; Schiestl, Robert

The use of radiation therapy is a cornerstone of modern cancer treatment. The number of patients that undergo radiation as a part of their therapy regimen is only increasing every year, but this does not come without cost. As this number increases, so too does the incidence of secondary, radiation-induced neoplasias, creating a need for therapeutic agents targeted specifically towards incidence reduction and treatment of these cancers. Development and efficacy testing of these agents requires [...]

Mené sur 488 patientes atteintes d'un cancer du sein HER2+, cet essai évalue les préférences des patientes pour le mode d'administration du trastuzumab, en injection sous-cutanée ou intra-veineuse, dans le cadre d'un traitement adjuvant

Patients' preferences for subcutaneous trastuzumab versus conventional intravenous infusion for the adjuvant treatment of HER2-positive early breast cancer: final analysis of 488 patients in the international, randomized, two-cohort PrefHer study

Pivot, X. ; Gligorov, J. ; Muller, V. ; Curigliano, G. ; Knoop, A. ; Verma, S. ; Jenkins, V. ; Scotto, N. ; Osborne, S. ; Fallowfield, L.

Background : Patients with HER2-positive early breast cancer (EBC) preferred subcutaneous (SC) trastuzumab, delivered via single-use injection device (SID), over the intravenous (IV) formulation (Cohort 1 of the PrefHer study: NCT01401166). Here we report patient preference, healthcare professional satisfaction, and safety data pooled from Cohort 1 and also Cohort 2, where SC trastuzumab was delivered via hand-held syringe. Patients and Methods : Patients were randomized to receive 4 adjuvant [...]