Menée sur 15 patients atteints d'un rétinoblastome intraoculaire traité entre 2006 et 2012 (durée médiane de suivi : 19 mois), cette étude évalue l'efficacité, du point de vue de la survie oculaire, et la toxicité d'une curiethérapie adjuvante ou de sauvetage après une chimiothérapie délivrée via l'artère ophtalmique

Salvage/Adjuvant Brachytherapy After Ophthalmic Artery Chemosurgery for Intraocular Retinoblastoma

Francis, Jasmine H. ; Barker, Christopher A. ; Wolden, Suzanne L. ; McCormick, Beryl ; Segal, Kira ; Cohen, Gil ; Gobin, Y. Pierre ; Marr, Brian P. ; Brodie, Scott E. ; Dunkel, Ira J. ; Abramson, David H.

To evaluate the efficacy and toxicity of brachytherapy after ophthalmic artery chemosurgery (OAC) for retinoblastoma. This was a single-arm, retrospective study of 15 eyes in 15 patients treated with OAC followed by brachytherapy at (blinded institution) between May 1, 2006, and December 31, 2012, with a median 19 months' follow-up from plaque insertion. Outcome measurements included patient and ocular survival, visual function, and retinal toxicity measured by electroretinogram (ERG). [...]

A partir de données des registres américains et de la base d'assurance maladie Medicare portant sur 3 986 patients atteints d'un cancer du poumon non à petites cellules de stade III diagnostiqué entre 2001 et 2007 (âgé : 66 ans ou plus), cette étude évalue la toxicité de la radiothérapie avec modulation d'intensité et identifie les facteurs associés à son utilisation

Intensity Modulated Radiotherapy for Stage III Non-Small Cell Lung Cancer in the United States : Predictors of Use and Association with Toxicities

Shirvani, Shervin M. ; Jiang, Jing ; Gomez, Daniel R. ; Chang, Joe Y. ; Buchholz, Thomas A. ; Smith, Benjamin D.

Background : Intensity modulated radiotherapy for stage III lung cancer has become commonplace in the United States in the absence of randomized controlled trials. We used a large, population-based database to determine which factors led to increased utilization of IMRT and to evaluate associations of IMRT with toxicities. Methods : The Surveillance, Epidemiology, and End Results (SEER)-Medicare records identified 3,986 individuals aged 66 years or older diagnosed with stage III lung cancer [...]

Menée à partir des données 1988-2005 des registres américains du cancer et de la base Medicare portant sur 67 087 patients atteints d'un cancer localisé de la prostate, cette étude compare, du point de vue de la survie globale et en fonction de l'espérance de vie du patient, l'efficacité de la prostatectomie radicale, de la radiothérapie et de la surveillance médicale

Radical prostatectomy vs radiotherapy vs observation among older patients with clinically localized prostate cancer: a comparative effectiveness evaluation

Sun, Maxine ; Sammon, Jesse D. ; Becker, Andreas ; Roghmann, Florian ; Tian, Zhe ; Kim, Simon P. ; Larouche, Alexandre ; Abdollah, Firas ; Hu, Jim C. ; Karakiewicz, Pierre I. ; Trinh, Quoc-Dien

Objective : To compare efficacy between radical prostatectomy (RP), radiotherapy and observation with respect to overall survival (OS) in patients with clinically localized prostate cancer (PCa). Methods : Using data (1988–2005) from the Surveillance, Epidemiology, and End Results–Medicare linked database, 67 087 men with localized PCa were identified. The prevalence of the initial treatment strategy was quantified according to patients' life expectancy ([LE] <10 vs ≥10 years) at initial [...]

Cet article fait le point sur les options thérapeutiques de sauvetage après récidive intraprostatique d'un cancer traité par radiothérapie externe

Salvage therapy of intraprostatic failure after radical external-beam radiotherapy for prostate cancer: A review

Alongi, Filippo ; De Bari, Berardino ; Campostrini, Franco ; Arcangeli, Stefano ; Matei, Deliu Victor ; Lopci, Egesta ; Petralia, Giuseppe ; Bellomi, Massimo ; Chiti, Arturo ; Magrini, Stefano Maria ; Scorsetti, Marta ; Orecchia, Roberto ; Jereczek-Fossa, Barbara Alicja

Radical external-beam radiotherapy (EBRT) is a standard treatment for prostate cancer (PC) patients. Despite this, the rate of intraprostatic relapses after primary EBRT is still not negligible. There is no consensus on the most appropriate management of these patients after EBRT failure. Treatment strategies after PC relapse are strongly influenced by the effective site of the tumor recurrence, and thus the instrumental evaluation with different imaging techniques becomes crucial. In cases of [...]

A partir d'une revue de la littérature publiée jusqu'en janvier 2013 (7 études, 766 patients), cette méta-analyse évalue, à partir de données intra- et péri- opératoires, l'intérêt d'une néphrectomie partielle assistée par robot par rapport à une néphrectomie partielle laparoscopique chez les patients atteints d'un cancer du rein

Comparison of peri-operative outcomes of robot-assisted vs laparoscopic partial nephrectomy: a meta-analysis

Zhang, Xiaohua ; Shen, Zhoujun ; Zhong, Shan ; Zhu, Zhaowei ; Wang, Xianjin ; Xu, Tianyuan

Objective : To conduct a meta-analysis of the literature on the peri-operative outcomes of both robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN). Materials and Methods : An electronic database search of MEDLINE, EMBASE, Google Scholar and the Cochrane Library was performed for publications up to 8 January 2013. * All studies comparing RAPN with LPN were included. The outcome measures were demographic and peri-operative results, including operating time, warm [...]

Cet article passe en revue les études concernant l'efficacité de stratégies chirurgicales pour traiter un craniopharyngiome et identifie les facteurs associés à une récidive

Surgical strategies and modern therapeutic options in the treatment of craniopharyngiomas

Mortini, Pietro ; Gagliardi, Filippo ; Boari, Nicola ; Losa, Marco

Abstract The optimal treatment of patients with craniopharyngioma remains controversial. In particular, the role of aggressive treatment compared to less aggressive therapeutic options is poorly understood. Radical resection is the therapy of choice at any age, because it is associated with the best outcome in terms of survival. Nevertheless, aggressive behaviour, location, involvement of critical structures, tumour size, calcifications, and patient age may limit the extent of resection. [...]

Menée sur 52 patients atteints d'un carcinome in situ de la vessie traité entre 1971 et 2008 (durée médiane de suivi : 8,5 ans), cette étude évalue, du point de vue du taux de survie sans récidive et du taux de survie globale à 5 et 10 ans, l'efficacité d'une cystectomie radicale

Outcome in patients with exclusive carcinoma in situ (CIS) after radical cystectomy

Zehnder, Pascal ; Moltzahn, Felix ; Daneshmand, Siamak ; Leahy, Marya ; Cai, Jie ; Miranda, Gus ; Bartsch, Georg ; Mitra, Anirban P. ; Skinner, Donald G. ; Skinner, Eila C. ; Gill, Inderbir S.

Objective : To evaluate oncological outcomes of patients with carcinoma in situ (CIS) exclusively at radical cystectomy (RC) and no previous history of ≥T1 disease. Patients and Methods : Patients undergoing RC with curative intent for CIS between 1971 and 2008 at the University of Southern California were included if they met all the following criteria: (i) pathological CIS-only disease at RC, (ii) preoperative clinical stage cCIS and/or cCIS + cTa, and (iii) no previous history of lamina [...]

Menée in vitro et à l'aide d'un modèle murin du processus métastatique, cette étude évalue le pourcentage des cellules néoplasiques exprimant un transgène à la suite d'une thérapie génique à base de nanoparticules de type CPS

A nanoparticle formulation that selectively transfects metastatic tumors in mice

Yang, Jian ; Hendricks, William ; Liu, Guosheng ; McCaffery, J. Michael ; Kinzler, Kenneth W. ; Huso, David L. ; Vogelstein, Bert ; Zhou, Shibin

Nanoparticle gene therapy holds great promise for the treatment of malignant disease in light of the large number of potent, tumor-specific therapeutic payloads potentially available for delivery. To be effective, gene therapy vehicles must be able to deliver their therapeutic payloads to metastatic lesions after systemic administration. Here we describe nanoparticles comprised of a core of high molecular weight linear polyethylenimine (LPEI) complexed with DNA and surrounded by a shell of [...]

Menée in vitro et à l'aide de xénogreffes, cette étude évalue la faisabilité de combiner deux technologies, à base de cellules souches pluripotentes induites et de récepteurs d'antigènes chimériques, pour disposer à volonté de lymphocytes T ciblés sur CD19

Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy

Themeli, Maria ; Kloss, Christopher C. ; Ciriello, Giovanni ; Fedorov, Victor D. ; Perna, Fabiana ; Gonen, Mithat ; Sadelain, Michel

Progress in adoptive T-cell therapy for cancer and infectious diseases is hampered by the lack of readily available, antigen-specific, human T lymphocytes. Pluripotent stem cells could provide an unlimited source of T lymphocytes, but the therapeutic potential of human pluripotent stem cell–derived lymphoid cells generated to date remains uncertain. Here we combine induced pluripotent stem cell (iPSC) and chimeric antigen receptor (CAR) technologies to generate human T cells targeted to CD19, [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en perturbant la fonction des cellules T régulatrices surexprimant Foxp3, l'inhibition d'une histone acétyltransférase, p300, favorise l'immunité antitumorale

Inhibition of p300 impairs Foxp3+ T regulatory cell function and promotes antitumor immunity

Liu, Yujie ; Wang, Liqing ; Predina, Jarrod ; Han, Rongxiang ; Beier, Ulf H. ; Wang, Liang-Chuan S. ; Kapoor, Veena ; Bhatti, Tricia R. ; Akimova, Tatiana ; Singhal, Sunil ; Brindle, Paul K. ; Cole, Philip A. ; Albelda, Steven M. ; Hancock, Wayne W.

Forkhead box P3 (Foxp3)+ T regulatory (Treg) cells maintain immune homeostasis and limit autoimmunity but can also curtail host immune responses to various types of tumors1, 2. Foxp3+ Treg cells are therefore considered promising targets to enhance antitumor immunity, and approaches for their therapeutic modulation are being developed. However, although studies showing that experimentally depleting Foxp3+ Treg cells can enhance antitumor responses provide proof of principle, these studies lack [...]

Cet article passe en revue les perspectives offertes par le développement d'agents ciblant un sphingolipide, la spingosine-1 phosphate, pour le traitement des cancers et des maladies inflammatoires

Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond

Kunkel, Gregory T. ; Maceyka, Michael ; Milstien, Sheldon ; Spiegel, Sarah

The bioactive lipid sphingosine-1-phosphate (S1P) is involved in multiple cellular signalling systems and has a pivotal role in the control of immune cell trafficking. As such, S1P has been implicated in disorders such as cancer and inflammatory diseases. This Review discusses the ways in which S1P might be therapeutically targeted — for example, via the development of chemical inhibitors that target the generation, transport and degradation of S1P and via the development of specific S1P [...]

Menée in vitro et in vivo, cette étude identifie un peptide d'une protéine musculaire impliqué dans la toxicité observée lors des essais cliniques d'une thérapie adoptive mettant en œuvre des lymphocytes T ciblant l'antigène MAGE A3

Identification of a Titin-Derived HLA-A1–Presented Peptide as a Cross-Reactive Target for Engineered MAGE A3–Directed T Cells

Cameron, Brian J. ; Gerry, Andrew B. ; Dukes, Joseph ; Harper, Jane V. ; Kannan, Vivekanandan ; Bianchi, Frayne C. ; Grand, Francis ; Brewer, Joanna E. ; Gupta, Minnal ; Plesa, Gabriela ; Bossi, Giovanna ; Vuidepot, Annelise ; Powlesland, Alex S. ; Legg, Alison ; Adams, Katherine J. ; Bennett, Alan D. ; Pumphrey, Nicholas J. ; Williams, Daniel D. ; Binder-Scholl, Gwendolyn ; Kulikovskaya, Irina ; Levine, Bruce L. ; Riley, James L. ; Varela-Rohena, Angel ; Stadtmauer, Edward A. ; Rapoport, Aaron P. ; Linette, Gerald P. ; June, Carl H. ; Hassan, Namir J. ; Kalos, Michael ; Jakobsen, Bent K.

MAGE A3, which belongs to the family of cancer-testis antigens, is an attractive target for adoptive therapy given its reactivation in various tumors and limited expression in normal tissues. We developed an affinity-enhanced T cell receptor (TCR) directed to a human leukocyte antigen (HLA)–A*01–restricted MAGE A3 antigen (EVDPIGHLY) for use in adoptive therapy. Extensive preclinical investigations revealed no off-target antigen recognition concerns; nonetheless, administration to patients of T [...]

Menée à l'aide de modèle murins, cette étude suggère l'intérêt d'antagonistes des récepteurs de l'adénosine (A2A ou A2B) pour prévenir le processus métastatique de tumeurs surexprimant CD73

Blockade of A2A receptors potently suppresses the metastasis of CD73+ tumors

Beavis, Paul A. ; Divisekera, Upulie ; Paget, Christophe ; Chow, Melvyn T. ; John, Liza B. ; Devaud, Christel ; Dwyer, Karen ; Stagg, John ; Smyth, Mark J. ; Darcy, Phillip K.

CD73 inhibits antitumor immunity through the activation of adenosine receptors expressed on multiple immune subsets. CD73 also enhances tumor metastasis, although the nature of the immune subsets and adenosine receptor subtypes involved in this process are largely unknown. In this study, we revealed that A2A/A2B receptor antagonists were effective in reducing the metastasis of tumors expressing CD73 endogenously (4T1.2 breast tumors) and when CD73 was ectopically expressed (B16F10 melanoma). [...]

Menée à l'aide de modèles murins, puis sur 32 patients atteints d'un cancer du poumon non à petites cellules, cette étude évalue l'activité antitumorale d'un nouvel agent anti-angiogénique, un anticorps anti EGFL7

Anti-EGFL7 antibodies enhance stress-induced endothelial cell death and anti-VEGF efficacy

Johnson, Leisa ; Huseni, Mahrukh ; Smyczek, Tanya ; Lima, Anthony ; Yeung, Stacey ; Cheng, Jason H. ; Molina, Rafael ; Kan, David ; De, Mazi ; xE, ; re, Ann ; Klumperman, Judith ; Kasman, Ian ; Zhang, Yin ; Dennis, Mark S. ; Eastham-Anderson, Jeffrey ; Jubb, Adrian M. ; Hwang, Olivia ; Desai, Rupal ; Schmidt, Maike ; Nannini, Michelle A. ; Barck, Kai H. ; Carano, Richard A. D. ; Forrest, William F. ; Song, Qinghua ; Chen, Daniel S. ; Naumovski, Louie ; Singh, Mallika ; Ye, Weilan ; Hegde, Priti S.

Many oncology drugs are administered at their maximally tolerated dose without the knowledge of their optimal efficacious dose range. In this study, we describe a multifaceted approach that integrated preclinical and clinical data to identify the optimal dose for an antiangiogenesis agent, anti-EGFL7. EGFL7 is an extracellular matrix–associated protein expressed in activated endothelium. Recombinant EGFL7 protein supported EC adhesion and protected ECs from stress-induced apoptosis. Anti-EGFL7 [...]

Menée in vitro, cette étude met en évidence des mécanismes par lesquels la sous-expression de MUC1-1 permet de contourner la résistance au trastuzumab de cellules de cancer du sein HER2+

Targeting the MUC1-C oncoprotein downregulates HER2 activation and abrogates trastuzumab resistance in breast cancer cells

Raina, D. ; Uchida, Y. ; Kharbanda, A. ; Rajabi, H. ; Panchamoorthy, G. ; Jin, C. ; Kharbanda, S. ; Scaltriti, M. ; Baselga, J. ; Kufe, D.

Patients with HER2-positive breast cancer often exhibit intrinsic or acquired resistance to trastuzumab treatment. The transmembrane mucin 1 (MUC1) oncoprotein is aberrantly overexpressed in breast cancer cells and associates with HER2. The present studies demonstrate that silencing MUC1 C-terminal subunit (MUC1-C) in HER2-overexpressing SKBR3 and BT474 breast cancer cells results in the downregulation of constitutive HER2 activation. Moreover, treatment with the MUC1-C inhibitor, GO-203, was [...]

Menée à l'aide d'un modèle murin de cancer du sein surexprimant HER2 et PI3KCA, cette étude met en évidence le rôle joué par l'activation aberrante de la signalisation PI3K dans la croissance tumorale et la résistance au trastuzumab, seul ou en combinaison avec le lapatinib ou le pertuzumab

Mutant PIK3CA accelerates HER2-driven transgenic mammary tumors and induces resistance to combinations of anti-HER2 therapies

Hanker, Ariella B. ; Pfefferle, Adam D. ; Balko, Justin M. ; Kuba, María Gabriela ; Young, Christian D. ; Sánchez, Violeta ; Sutton, Cammie R. ; Cheng, Hailing ; Perou, Charles M. ; Zhao, Jean J. ; Cook, Rebecca S. ; Arteaga, Carlos L.

Human epidermal growth factor receptor 2 (HER2; ERBB2) amplification and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations often co-occur in breast cancer. Aberrant activation of the phosphatidylinositol 3-kinase (PI3K) pathway has been shown to correlate with a diminished response to HER2-directed therapies. We generated a mouse model of HER2-overexpressing (HER2+), PIK3CAH1047R-mutant breast cancer. Mice expressing both human HER2 and mutant PIK3CA in [...]

Menée à l'aide de modèles murins de glioblastome, cette étude évalue l'activité antitumorale d'un composé appelé MPS1-IN-3, un inhibiteur sélectif de la kinase MPS1, en combinaison avec la vincristine

Effects of the Selective MPS1 Inhibitor MPS1-IN-3 on Glioblastoma Sensitivity to Antimitotic Drugs

Tannous, Bakhos A. ; Kerami, Mariam ; Van der Stoop, Petra M. ; Kwiatkowski, Nicholas ; Wang, Jinhua ; Zhou, Wenjun ; Kessler, Almuth F. ; Lewandrowski, Grant ; Hiddingh, Lotte ; Sol, Nik ; Lagerweij, Tonny ; Wedekind, Laurine ; Niers, Johanna M. ; Barazas, Marco ; Nilsson, R. Jonas A. ; Geerts, Dirk ; De Witt Hamer, Philip C. ; Hagemann, Carsten ; Vandertop, W. Peter ; Van Tellingen, Olaf ; Noske, David P. ; Gray, Nathanael S. ; Wurdinger, Thomas

Background Glioblastomas exhibit a high level of chemotherapeutic resistance, including to the antimitotic agents vincristine and taxol. During the mitotic agent-induced arrest, glioblastoma cells are able to perform damage-control and self-repair to continue proliferation. Monopolar spindle 1 (MPS1/TTK) is a checkpoint kinase and a gatekeeper of the mitotic arrest. Methods We used glioblastoma cells to determine the expression of MPS1 and to determine the effects of MPS1 inhibition on mitotic [...]

En complément de travaux in vitro et in vivo, cet essai de phase I évalue l'intérêt d'utiliser l'azacitidine pour surmonter la résistance à la doxorubicine chez les patients atteints d'un lymphome diffus à grandes cellules B à haut risque

Mechanism-Based Epigenetic Chemosensitization Therapy of Diffuse Large B-Cell Lymphoma

Clozel, Thomas ; Yang, ShaoNing ; Elstrom, Rebecca L. ; Tam, Wayne ; Martin, Peter ; Kormaksson, Matthias ; Banerjee, Samprit ; Vasanthakumar, Aparna ; Culjkovic, Biljana ; Scott, David W. ; Wyman, Sarah ; Leser, Micheal ; Shaknovich, Rita ; Chadburn, Amy ; Tabbo, Fabrizio ; Godley, Lucy A. ; Gascoyne, Randy D. ; Borden, Katherine L. ; Inghirami, Giorgio ; Leonard, John P. ; Melnick, Ari ; Cerchietti, Leandro

Although aberrant DNA methylation patterning is a hallmark of cancer, the relevance of targeting DNA methyltransferases (DNMT) remains unclear for most tumors. In diffuse large B-cell lymphoma (DLBCL) we observed that chemoresistance is associated with aberrant DNA methylation programming. Prolonged exposure to low-dose DNMT inhibitors (DNMTI) reprogrammed chemoresistant cells to become doxorubicin sensitive without major toxicity in vivo. Nine genes were recurrently hypermethylated in [...]

Mené sur 92 patients atteints d'un mélanome métastatique avec mutation du gène BRAF (76 avec la mutation V600 E,16 avec la mutation V600E/K mut+ MM), cet essai de phase II évalue la toxicité et l'activité clinique du dabrafenib

Phase II Trial (BREAK-2) of the BRAF Inhibitor Dabrafenib (GSK2118436) in Patients With Metastatic Melanoma

Ascierto, Paolo A. ; Minor, David ; Ribas, Antoni ; Lebbé, Celeste ; O’Hagan, Anne ; Arya, Niki ; Guckert, Mary ; Schadendorf, Dirk ; Kefford, Richard F. ; Grob, Jean-Jacques ; Hamid, Omid ; Amaravadi, Ravi ; Simeone, Ester ; Wilhelm, Tabea ; Kim, Kevin B. ; Long, Georgina V. ; Martin, Anne-Marie ; Mazumdar, Jolly ; Goodman, Vicki L. ; Trefzer, Uwe

Purpose Dabrafenib (GSK2118436) is a potent inhibitor of mutated BRAF kinase. Our multicenter, single-arm, phase II study assessed the safety and clinical activity of dabrafenib in BRAFV600E/K mutation–positive metastatic melanoma (mut+ MM). Patients and Methods Histologically confirmed patients with stage IV BRAFV600E/K mut+ MM received oral dabrafenib 150 mg twice daily until disease progression, death, or unacceptable adverse events (AEs). The primary end point was investigator-assessed [...]

Mené sur 637 patientes atteintes d'un cancer épithélial de l'ovaire, de la trompe de Fallope ou du péritoine, cet essai japonais compare, du point de vue de la survie sans progression, l'efficacité d'un schéma dose-dense de paclitaxel et carboplatine avec un protocole conventionnel (durée médiane de suivi : 76,8 mois)

Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial

Katsumata, Noriyuki ; Yasuda, Makoto ; Isonishi, Seiji ; Takahashi, Fumiaki ; Michimae, Hirofumi ; Kimura, Eizo ; Aoki, Daisuke ; Jobo, Toshiko ; Kodama, Shoji ; Terauchi, Fumitoshi ; Sugiyama, Toru ; Ochiai, Kazunori

Background : The primary analysis of the JGOG 3016 trial showed that a dose-dense paclitaxel and carboplatin regimen significantly improves progression-free and overall survival compared with the conventional regimen as first-line chemotherapy for patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. We report the long-term follow-up results for survival. Methods : This randomised controlled trial was done at 85 centres in Japan. Patients with stage II—IV ovarian [...]

Cet article passe en revue les travaux récents sur la prise en charge des patients atteints d'un cancer du poumon non à petites cellules

Management of non-small-cell lung cancer: recent developments

Reck, Martin ; Heigener, David F. ; Mok, Tony ; Soria, Jean-Charles ; Rabe, Klaus F.

Non-small-cell lung cancer is one of the leading causes of deaths from cancer worldwide. Therefore, improvements in diagnostics and treatments are urgently needed. In this review, we will discuss the evolution of lung cancer staging towards more non-invasive, endoscopy-based, and image-based methods, and the development of stage-adapted treatment. A special focus will be placed on the role of novel surgical approaches and modern radiotherapy strategies for early stages of disease, the effect of [...]

Mené sur 1 110 patients atteints d'un carcinome rénal métastatique à cellules claires, cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression, et la toxicité du pazopanib et du sunitinib

Pazopanib versus Sunitinib in Metastatic Renal-Cell Carcinoma

Motzer, Robert J. ; Hutson, Thomas E. ; Cella, David ; Reeves, James ; Hawkins, Robert ; Guo, Jun ; Nathan, Paul ; Staehler, Michael ; de Souza, Paul ; Merchan, Jaime R. ; Boleti, Ekaterini ; Fife, Kate ; Jin, Jie ; Jones, Robert ; Uemura, Hirotsugu ; De Giorgi, Ugo ; Harmenberg, Ulrika ; Wang, Jinwan ; Sternberg, Cora N. ; Deen, Keith ; McCann, Lauren ; Hackshaw, Michelle D. ; Crescenzo, Rocco ; Pandite, Lini N. ; Choueiri, Toni K.

Background : Pazopanib and sunitinib provided a progression-free survival benefit, as compared with placebo or interferon, in previous phase 3 studies involving patients with metastatic renal-cell carcinoma. This phase 3, randomized trial compared the efficacy and safety of pazopanib and sunitinib as first-line therapy. Methods : We randomly assigned 1110 patients with clear-cell, metastatic renal-cell carcinoma, in a 1:1 ratio, to receive a continuous dose of pazopanib (800 mg once daily; 557 [...]

Mené sur 4 894 patientes atteintes d'un cancer du sein de stade précoce avec envahissement ganglionnaire, cet essai de phase III compare l'efficacité, du point de vue de la survie sans maladie à 5 ans, et la toxicité de trois protocoles de chimiothérapie en traitement adjuvant

Definitive Results of a Phase III Adjuvant Trial Comparing Three Chemotherapy Regimens in Women With Operable, Node-Positive Breast Cancer: The NSABP B-38 Trial

Swain, Sandra M. ; Tang, Gong ; Geyer, Charles E. ; Rastogi, Priya ; Atkins, James N. ; Donnellan, Paul P. ; Fehrenbacher, Louis ; Azar, Catherine A. ; Robidoux, André ; Polikoff, Jonathan A. ; Brufsky, Adam M. ; Biggs, David D. ; Levine, Edward A. ; Zapas, John L. ; Provencher, Louise ; Northfelt, Donald W. ; Paik, Soonmyung ; Costantino, Joseph P. ; Mamounas, Eleftherios P. ; Wolmark, Norman

Purpose Anthracycline- and taxane-based three-drug chemotherapy regimens have proven benefit as adjuvant therapy for early-stage breast cancer. This trial (NSABP B-38; Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Positive Breast Cancer) asked whether the incorporation of a fourth drug could improve outcomes relative to two standard regimens and provided a direct comparison of those two regimens. Patients and Methods We randomly assigned 4,894 women with [...]

Mené sur 325 patients atteints d'un glioblastome récidivant, cet essai de phase III évalue, du point de vue de la survie sans progression, l'efficacité du cédiranib, seul ou en combinaison avec la lomustine, après une radiothérapie et une chimiothérapie à base de témozolomide

Phase III Randomized Trial Comparing the Efficacy of Cediranib As Monotherapy, and in Combination With Lomustine, Versus Lomustine Alone in Patients With Recurrent Glioblastoma

Batchelor, Tracy T. ; Mulholland, Paul ; Neyns, Bart ; Nabors, L. Burt ; Campone, Mario ; Wick, Antje ; Mason, Warren ; Mikkelsen, Tom ; Phuphanich, Surasak ; Ashby, Lynn S. ; DeGroot, John ; Gattamaneni, Rao ; Cher, Lawrence ; Rosenthal, Mark ; Payer, Franz ; Jürgensmeier, Juliane M. ; Jain, Rakesh K. ; Sorensen, A. Gregory ; Xu, John ; Liu, Qi ; van den Bent, Martin

Purpose A randomized, phase III, placebo-controlled, partially blinded clinical trial (REGAL [Recentin in Glioblastoma Alone and With Lomustine]) was conducted to determine the efficacy of cediranib, an oral pan–vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, either as monotherapy or in combination with lomustine versus lomustine in patients with recurrent glioblastoma. Patients and Methods Patients (N = 325) with recurrent glioblastoma who previously received [...]

Menée sur 62 patients atteints d'un carcinome hépatocellulaire, cette étude évalue l'efficacité, du point de vue de la récidive et de la survie sans progression, et la toxicité d'un traitement combinant une ablation par radiofréquences et des séances d'immunothérapie cellulaire

Combination of radiofrequency ablation and sequential cellular immunotherapy improves progression-free survival for patients with hepatocellular carcinoma

Cui, Jiuwei ; Wang, Nanya ; Zhao, Hengjun ; Jin, Haofan ; Wang, Guanjun ; Niu, Chao ; Terunuma, Hiroshi ; He, Hua ; Li, Wei

Hepatocellular carcinoma (HCC) recurs frequently after minimally invasive therapy. The aim of our study was to observe the efficiency and safety of the combined treatment of radiofrequency ablation (RFA) with cellular immunotherapy (CIT) for HCC patients. In our study, 62 patients with HCC who were treated with radical RFA were divided into two groups: RFA alone (32 patients) and RFA/CIT (30 patients). Autologous mononuclear cells were collected from the peripheral blood and separated by [...]

A partir de données médicales portant sur 167 patients atteints d'un cancer primitif de l'œsophage traité par chimioradiothérapie concomitante entre 2001 et 2010 (durée médiane de suivi : 29 mois), cette étude évalue la dose de rayonnements ionisants associée au risque d'épanchement péricardique symptomatique

Symptomatic Pericardial Effusion After Chemoradiation Therapy in Esophageal Cancer Patients

Fukada, Junichi ; Shigematsu, Naoyuki ; Takeuchi, Hiroya ; Ohashi, Toshio ; Saikawa, Yoshiro ; Takaishi, Hiromasa ; Hanada, Takashi ; Shiraishi, Yutaka ; Kitagawa, Yuko ; Fukuda, Keiichi

We investigated clinical and treatment-related factors as predictors of symptomatic pericardial effusion in esophageal cancer patients after concurrent chemoradiation therapy. We reviewed 214 consecutive primary esophageal cancer patients treated with concurrent chemoradiation therapy between 2001 and 2010 in our institute. Pericardial effusion was detected on follow-up computed tomography. Symptomatic effusion was defined as effusion ≥grade 3 according to Common Terminology Criteria for [...]

Mené sur 64 patients atteints d'un cancer du poumon non à petites cellules de stade IIIA/IIIB (âge : 33 à 69 ans), cet essai multicentrique franco-allemand de phase II évalue la survie à 10 ans après un protocole thérapeutique comportant trois cycles d'une chimiothérapie d'induction par cisplatine/paclitaxel, une chimioradiothérapie concomitante par cisplatine/étoposide et un traitement chirurgical

10-year long-term survival (LTS) of induction chemotherapy with three cycles cisplatin/paclitaxel followed by concurrent chemoradiation cisplatin/etoposide/45Gy (1.5Gy bid) plus surgery in locally advanced non-small-cell lung cancer (NSCLC)—A multicenter phase-II trial (CISTAXOL)

Eberhardt, Wilfried Ernst Erich ; Gauler, Thomas Christoph ; LePechoux, Cecile ; Stamatis, Georgios ; Bildat, Stephan ; Krbek, Thomas ; Welter, Stefan ; Grunenwald, Dominique ; Fischer, Berthold ; Rodrigo, Hepp de los Rios ; Theegarten, Dirk ; Le Chevalier, Thierry ; Seeber, Siegfried ; Stuschke, Martin ; Poettgen, Christoph

Background : Induction chemoradiotherapy plus surgery remains an option to study in IIIA(N2) and selected IIIB NSCLC. Here we report ten-year long-term survival of a prospective multicenter German–French phase-II trial with trimodality. Patients and methods : Mediastinoscopically proven IIIA(N2)/selected IIIB NSCLC received three cycles cisplatin (50mg/m2 day 1+8) and paclitaxel (175mg/m2d1) qd 22. Concurrent CTx/RTx followed: 45Gy (1.5Gy bid) with cisplatin 50mg/m2 day 2+9 and etoposide [...]

Mené sur 98 patients atteints d'un cancer du poumon non à petites cellules inopérable de stade IIIA/B et traités entre juin 2007 et novembre 2009, cet essai de phase II évalue l'efficacité, du point de vue du taux de survie globale à 2 ans, d'un traitement comportant le pémétrexed, combiné au carboplatine ou au cisplatine, une radiothérapie concomitante et une chimiothérapie de consolidation par pémétrexed

Phase 2 Study of Pemetrexed Plus Carboplatin, or Pemetrexed Plus Cisplatin with Concurrent Radiation Therapy Followed by Pemetrexed Consolidation in Patients with Favorable-Prognosis Inoperable Stage IIIA/B Non-Small-Cell Lung Cancer

Choy, Hak ; Schwartzberg, Lee S. ; Dakhil, Shaker R. ; Garon, Edward B. ; Gerber, David E. ; Choksi, Janak K. ; Govindan, Ramaswamy ; Peng, Guangbin ; Koustenis, Andrew ; Treat, Joseph ; Obasaju, Coleman

Introduction : There is no consensus chemotherapy regimen with concurrent radiotherapy (RT) for inoperable stage IIIA/B non-small-cell lung cancer. This trial evaluated pemetrexed with carboplatin (PCb) or cisplatin (PC) with concurrent RT followed by consolidation pemetrexed. Methods : In this open-label, noncomparative phase II trial, patients with inoperable stage IIIA/B non-small-cell lung cancer (initially all histologies, later restricted to nonsquamous) were randomized (1:1) to PCb or PC [...]

Menée in vitro et à l'aide de xénogreffes de gliome, cette étude montre qu'un traitement combinant une radiothérapie fractionnée et un virus modifié codant pour un anticorps ciblant le facteur de croissance VEGF et sensibilisant l'endothélium tumoral aux rayonnements ionisants améliore le contrôle tumoral

Combination of fractionated irradiation with anti-VEGF expressing vaccinia virus therapy enhances tumor control by simultaneous radiosensitization of tumor associated endothelium

Buckel, Lisa ; Advani, Sunil J. ; Frentzen, Alexa ; Zhang, Qian ; Yu, Yong A. ; Chen, Nanhai G. ; Ehrig, Klaas ; Stritzker, Jochen ; Mundt, Arno J. ; Szalay, Aladar A.

Oncolytic viruses are currently in clinical trials for a variety of tumors, including high grade gliomas. A characteristic feature of high grade gliomas is their high vascularity and treatment approaches targeting tumor endothelium are under investigation, including bevacizumab. The aim of this study was to improve oncolytic viral therapy by combining it with ionizing radiation and to radiosensitize tumor vasculature through a viral encoded anti-angiogenic payload. Here, we show how vaccinia [...]

Menés sur 116 patients atteints d'un cancer rhinopharyngé de stade III ou IVA/IVB (durée médiane de suivi : 32,9 mois), deux essais évaluent l'efficacité, du point de vue du taux de survie sans progression et du taux de survie globale à 3 ans, et la toxicité d'un traitement comportant une chimiothérapie néoadjuvante par taxane-cisplatine-5-fluorouracile puis une chimioradiothérapie concomitante

Neoadjuvant chemotherapy followed by concurrent chemoradiation for locoregionally advanced nasopharyngeal carcinoma

Kong, Lin ; Hu, Chaosu ; Niu, Xiaoshuang ; Zhang, Youwang ; Guo, Ye ; Tham, Ivan W. K. ; Lu, Jiade Jay

BACKGROUND : The authors studied the efficacy of neoadjuvant chemotherapy, consisting of a taxane, cisplatin, and 5-fluorouracil (5-FU) (the TPF regimen) followed by concurrent chemoradiation, in 2 separately designed and synchronously executed phase 2 trials for stage III and IVA/IVB nasopharyngeal cancer (NPC). METHODS : Patients with newly diagnosed NPC were accrued to 2 trials, 1 for patients with stage III disease and the other for patients with IVA/IVB disease. All patients received TPF [...]