Menée à l'aide de modèles murins, cette étude évalue l'intérêt d'un vaccin, délivré par injection intratumorale, pour favoriser une réponse immunitaire contre les cellules stromales immunosuppressives dont le recrutement est induit par la radiothérapie

Enhanced cancer radiotherapy through immunosuppressive stromal cell destruction in tumors

Wu, Chao-Yi ; Yang, Li-Hua ; Yang, Huang-Yu ; Knoff, Jayne ; Peng, Shiwen ; Lin, Yi-Hsin ; Wang, Chenguang ; Alvarez, Ronald ; Pai, Sara I. ; Roden, Richard B.S. ; Hung, Chien-Fu ; Wu, T.-C.

Purpose: Radiation therapy (RT) kills cancer cells by causing DNA damage, and stimulates a systemic antitumor immune response by releasing tumor antigen and endogenous adjuvant within the tumor microenvironment. However, RT also induces the recruitment of immunosuppressive myeloid cells, which can interfere with the antitumor immune responses elicited by apoptotic tumor cells. We hypothesized that local delivery of vaccine following RT will lead to the priming of antigen-specific cytotoxic T [...]

Menée à l'aide d'un modèle murin, cette étude montre que la protéine adaptatrice Lnk (Sh2b3), en inhibant la signalisation de l'interleukine IL-11, supprime la résistance des cellules tumorales aux rayonnements ionisants et empêche le développement de tumeurs malignes à cellules B induit par la radiothérapie

Lnk adaptor suppresses radiation resistance and radiation-induced B-cell malignancies by inhibiting IL-11 signaling

Louria-Hayon, Igal ; Frelin, Catherine ; Ruston, Julie ; Gish, Gerald ; Jin, Jing ; Kofler, Michael M. ; Lambert, Jean-Philippe ; Adissu, Hibret A. ; Milyavsky, Michael ; Herrington, Robert ; Minden, Mark D. ; Dick, John E. ; Gingras, Anne-Claude ; Iscove, Norman N. ; Pawson, Tony

The Lnk (Sh2b3) adaptor protein dampens the response of hematopoietic stem cells and progenitors (HSPCs) to a variety of cytokines by inhibiting JAK2 signaling. As a consequence, Lnk−/− mice develop hematopoietic hyperplasia, which progresses to a phenotype resembling the nonacute phase of myeloproliferative neoplasm. In addition, Lnk mutations have been identified in human myeloproliferative neoplasms and acute leukemia. We find that Lnk suppresses the development of radiation-induced acute [...]

Menée in vitro et à l'aide d'un modèle murin, cette étude montre que l'internalisation cellulaire du facteur de croissance des fibroblastes12, administré par voie intrapéritonéale avant une radiothérapie, peut protéger l'intestin contre les dommages liés aux rayonnements ionisants, indépendamment de la signalisation du récepteur FGFR

Cellular Internalization of Fibroblast Growth Factor-12 Exerts Radioprotective Effects on Intestinal Radiation Damage Independently of FGFR Signaling

Nakayama, Fumiaki ; Umeda, Sachiko ; Yasuda, Takeshi ; Fujita, Mayumi ; Asada, Masahiro ; Meineke, Viktor ; Imamura, Toru ; Imai, Takashi

Purpose : Several fibroblast growth factors (FGFs) were shown to inhibit radiation-induced tissue damage through FGF receptor (FGFR) signaling; however, this signaling was also found to be involved in the pathogenesis of several malignant tumors. In contrast, FGF12 cannot activate any FGFRs. Instead, FGF12 can be internalized readily into cells using 2 cell-penetrating peptide domains (CPP-M, CPP-C). Therefore, this study focused on clarifying the role of FGF12 internalization in protection [...]

A partir d'une revue systématique de la littérature publiée jusqu'en septembre 2013 (7 études, 1 145 patients), cette méta-analyse compare, du point de vue de la survie globale à long terme, de la mortalité et de la morbidité péri-opératoires, l'efficacité d'une pneumonectomie extrapleurale et d'une pleurectomie avec décortication chez les patients atteints d'un mésothéliome pleural malin

A systematic review and meta-analysis of surgical treatments for malignant pleural mesothelioma

Cao, Christopher ; Tian, David ; Park, John ; Allan, James ; Pataky, Kristopher A. ; Yan, Tristan D.

Background : Malignant pleural mesothelioma (MPM) is an aggressive disease of the pleural lining with a dismal prognosis. Surgical treatments of MPM with a curative intent include extrapleural pneumonectomy and extended pleurectomy/decortication (P/D). This meta-analysis aimed to compare the perioperative and long-term outcomes of EPP and extended P/D for selected surgical candidates. Methods : A systematic review of the literature was performed on five electronic databases to identify all [...]

Menée sur 41 patients atteints d'une maladie de Paget extramammaire (durée médiane de suivi : 41 mois), cette étude évalue l'efficacité, du point de vue de l'absence de progression locale ou de maladie à 3 et 5 ans, et la toxicité d'une radiothérapie, puis identifie les facteurs pronostiques associés

Radiation therapy for extramammary Paget's disease: treatment outcomes and prognostic factors

Hata, M. ; Koike, I. ; Wada, H. ; Miyagi, E. ; Kasuya, T. ; Kaizu, H. ; Matsui, T. ; Mukai, Y. ; Ito, E. ; Inoue, T.

Background : Extramammary Paget's disease (EMPD) is a relatively rare malignancy, and there are few reports related to radiation therapy. In the present study, we investigated the outcome of radiation therapy for EMPD. Patients and methods : Forty-one patients with EMPD in the genitalia underwent radiation therapy with curative intent. Fifteen patients had regional lymph node metastases before radiation therapy, but none had distant metastasis. Total doses of 45–80.2 Gy (median, 60 Gy) were [...]

Menée au Royaume-Uni sur 1 038 patients atteints d'un cancer de la prostate à faible risque de récidive traité entre 2002 et 2007, cette étude multicentrique évalue, du point de vue du taux de survie sans récidive biochimique à 5 ans, l'efficacité d'une curiethérapie à faible débit de dose avec grains d'iode 125

Five-year outcomes after iodine-125 seed brachytherapy for low-risk prostate cancer at three cancer centres in the UK

Dickinson, Peter D. ; Malik, Jahangeer ; Mandall, Paula ; Swindell, Ric ; Bottomley, David ; Hoskin, Peter ; Logue, John P. ; Wylie, James P.

Objective : To report the outcomes of >1000 men with low-risk prostate cancer treated with low-dose-rate (LDR) brachytherapy at three large UK cancer centres. Patients and Methods : A total of 1038 patients with low-risk prostate cancer (prostate-specific antigen [PSA] ≤10 ng/mL, Gleason score 6, ≤T2b disease) were treated with LDR iodine 125 (I-125) brachytherapy between 2002 and 2007. Patients were treated at three UK centres. PSA and clinical follow-up was performed at each centre. [...]

Menée à partir de données médicales portant sur 13 268 patients atteints d'un cancer localisé de la prostate traité entre 1992 et 2011, cette étude européenne évalue, du point de vue de la récidive biochimique, de la continence urinaire et de la préservation de la fonction érectile, l'intérêt d'une prostatectomie radicale chez les patients âgés de moins de 50 ans (443 cas)

Functional and oncological outcomes of patients aged <50 years treated with radical prostatectomy for localised prostate cancer in a European population

Becker, Andreas ; Tennstedt, Pierre ; Hansen, Jens ; Trinh, Quoc-Dien ; Kluth, Luis ; Atassi, Nabil ; Schlomm, Thorsten ; Salomon, Georg ; Haese, Alexander ; Budaeus, Lars ; Michl, Uwe ; Heinzer, Hans ; Huland, Hartwig ; Graefen, Markus ; Steuber, Thomas

Objective : To address the biochemical and functional outcomes after radical prostatectomy (RP) of men aged <50 years in a large European population. Patients and Methods : Among 13 268 patients who underwent RP for clinically localised prostate cancer at our centre (1992–2011), 443 (3.3%) men aged <50 were identified. Biochemical recurrence (BCR) and functional outcomes (International Index of Erectile Function [IIEF-5], use of pads), were prospectively evaluated and compared between men aged [...]

Mené sur 83 patients atteints d'un sarcome rétropéritonéal (durée médiane de suivi : 4,8 ans), cet essai italien de phase I-II évalue, du point de vue de la survie sans récidive et de la survie globale à 3 et 5 ans, l'efficacité d'une chimioradiothérapie pré-opératoire par ifusfamide

Preoperative chemo-radiation therapy for localised retroperitoneal sarcoma: A phase I–II study from the Italian Sarcoma Group

Gronchi, Alessandro ; De Paoli, Antonino ; Dani, Carla ; Merlo, Domenico Franco ; Quagliuolo, Vittorio ; Grignani, Giovanni ; Bertola, Giulio ; Navarria, Piera ; Sangalli, Claudia ; Buonadonna, Angela ; De Sanctis, Rita ; Sanfilippo, Roberta ; Dei Tos, Angelo Paolo ; Stacchiotti, Silvia ; Giorello, Laura ; Fiore, Marco ; Bruzzi, Paolo ; Casali, Paolo Giovanni

Background : To study feasibility, safety and activity of the combination of high-dose long-infusion ifosfamide (HLI) and radiotherapy (RT) as preoperative treatment for resectable localised retroperitoneal sarcoma (RPS). Methods : Patients received three cycles of HLI (14 g/m2). RT was started in combination with second cycle and administered up to a total dose of 50.4 Gy. Surgery was scheduled 4–6 weeks after the end of RT. Primary end-point was 3-year relapse free survival (RFS). The trial [...]

Cet article passe en revue les avancées récentes et les controverses concernant l'utilisation de la radiothérapie pour traiter un cancer invasif du sein

Progress and controversies: Radiation therapy for invasive breast cancer

Jagsi, Reshma

Answer questions and earn CME/CNE Radiation therapy is a critical component of the multidisciplinary management of invasive breast cancer. In appropriately selected patients, radiation not only improves local control, sparing patients the morbidity and distress of local recurrence, but it also improves survival by preventing seeding and reseeding of distant metastases from persistent reservoirs of locoregional disease. In recent years, considerable progress has been made toward improving our [...]

Mené sur 517 patientes atteintes d'un cancer du sein de stade T1N0 traité par quadrantectomie entre 1998 et 2003 (âge : 30 à 65 ans ; durée médiane de suivi supérieure à 10 ans), cet essai randomisé évalue, du point de vue de la survie sans maladie et de la survie globale, l'intérêt d'un curage ganglionnaire axillaire

Axillary lymph node dissection versus no dissection in patients with T1N0 breast cancer: A randomized clinical trial (INT09/98)

Agresti, Roberto ; Martelli, Gabriele ; Sandri, Marco ; Tagliabue, Elda ; Carcangiu, Maria Luisa ; Maugeri, Ilaria ; Pellitteri, Cristina ; Ferraris, Cristina ; Capri, Giuseppe ; Moliterni, Angela ; Bianchi, Giulia ; Mariani, Gabriella ; Trecate, Giovanna ; Lozza, Laura ; Langer, Martin ; Rampa, Mario ; Gennaro, Massimiliano ; Greco, Marco ; Menard, Sylvie ; Pierotti, Marco A.

BACKGROUND : Although axillary surgery is still considered to be a fundamental part of the management of early breast cancer, it may no longer be necessary either as treatment or as a guide to adjuvant treatment. The authors conducted a single-center randomized trial (INT09/98) to determine the impact of avoiding axillary surgery in patients with T1N0 breast cancer and planning chemotherapy based on biological factors of the primary tumor on long-term disease control. METHODS : From June 1998 [...]

Menée à partir de données portant sur 30 patients atteints d'un cholangiocarcinome extra-hépatique non résécable de stade localement avancé (durée médiane de suivi : 12 mois), cette étude française évalue l'efficacité, du point de vue de la survie sans progression à 1 et 3 ans, et la toxicité d'une radiothérapie externe conformationnelle 3D en combinaison ou non avec une chimiothérapie

Impact of radiotherapy in the management of locally advanced extrahepatic cholangiocarcinoma

Moureau-Zabotto, Laurence ; Turrini, Olivier ; Resbeut, Michel ; Raoul, Jean-Luc ; Giovannini, Marc ; Poizat, Flora ; Piana, Gilles ; Delpero, Jean-Robert ; Bertucci, François

Objectives : Optimal therapy for patients with unresectable locally advanced extrahepatic cholangiocarcinoma (ULAC) remains controversial. We analysed the role of radiotherapy in the management of such tumors. Methods : We retrospectively reviewed the charts of patients treated in our institution with conformal-3D external-beam-radiotherapy (EBRT) with or without concurrent chemotherapy. Results : Thirty patients were included: 24 with a primary tumor (group1) and 6 with a local relapse [...]

Mené sur 19 chiens ayant développé spontanément un lymphome diffus à grandes cellules B, cet essai randomisé évalue l'efficacité, du point de vue de la période avant progression et de la survie spécifique, et la toxicité d'une vaccination autologue en combinaison avec une chimiothérapie

Randomized, placebo-controlled, double-blinded chemo-immunotherapy clinical trial in a Pet Dog model of Diffuse Large B-cell Lymphoma

Marconato, Laura ; Frayssinet, Patrick ; Rouquet, Nicole ; Comazzi, Stefano ; Leone, Vito F ; Laganga, Paola ; Rossi, Federica ; Vignoli, Massimo ; Pezzoli, Lorenzo ; Aresu, Luca

Purpose: Active immunotherapy is a promising antitumoral strategy; however its use in combination with chemotherapy in dogs with large B-cell lymphoma (DLBCL) remains largely untested. Heat shock proteins (HSPs) bind the small peptides they chaperone (HSPPCs), allowing for immunization of the host against a large repertoire of tumor-associated antigens. Hydroxylapatite (HA) vehicles HSPPCs and acts as an immunologic adjuvant. Aim of this study was to show that an autologous vaccine with HA and [...]

Menée in vitro et in vivo sur des modèles de myélome multiple, cette étude met en évidence des mécanismes par lesquels une molécule appelée b-AP15, un inhibiteur de deux enzymes de déubiquitylation, permet de surmonter une résistance au bortézomib

A novel small molecule inhibitor of deubiquitylating enzyme USP14 and UCHL5 induces apoptosis in multiple myeloma and overcomes bortezomib resistance

Tian, Ze ; D'Arcy, Padraig ; Wang, Xin ; Ray, Arghya ; Tai, Yu-Tzu ; Hu, Yiguo ; Carrasco, Ruben D. ; Richardson, Paul ; Linder, Stig ; Chauhan, Dharminder ; Anderson, Kenneth C.

Proteasome inhibitors have demonstrated that targeting protein degradation is effective therapy in multiple myeloma (MM). Here we show that deubiquitylating enzymes (DUBs) USP14 and UCHL5 are more highly expressed in MM cells than in normal plasma cells. USP14 and UCHL5 siRNA knockdown decrease MM cell viability. A novel 19S regulatory particle inhibitor b-AP15 selectively blocks deubiquitylating activity of USP14 and UCHL5 without inhibiting proteasome activity. b-AP15 decreases viability in [...]

Cet article passe en revue les travaux récents sur le développement de nouvelles stratégies thérapeutiques, notamment à l'aide de trabectedine en combinaison avec la doxorubicine liposomale pégylée, pour le traitement des patientes atteintes d'un cancer de l'ovaire ayant développé une résistance aux chimiothérapies à base de taxanes et sels de platine

Emerging treatment strategies in recurrent platinum-sensitive ovarian cancer: Focus on trabectedin

Poveda, Andres ; Ray-Coquard, Isabelle ; Romero, Ignacio ; Lopez-Guerrero, Jose Antonio ; Colombo, Nicoletta

Ovarian cancer (OC) is the leading cause of death from gynecological malignancies. In spite of high response rates to the standard front-line treatment for advanced disease with cytoreductive surgical debulking, followed by platinum/taxane-based chemotherapy, most patients eventually relapse developing drug-resistant disease. Owing to the molecular heterogeneity, genetic instability and mutagenicity of OC, increases in survival might be achieved by translating recent insights at the [...]

Menée in vitro et in vivo, cette étude évalue les performances d'un système appelé LODER permettant d'acheminer un petit ARN interférent ciblant le gène KRAS muté dans les tumeurs pancréatiques

Mutant KRAS is a druggable target for pancreatic cancer

Zorde Khvalevsky, Elina ; Gabai, Racheli ; Rachmut, Itzhak Haim ; Horwitz, Elad ; Brunschwig, Zivia ; Orbach, Ariel ; Shemi, Adva ; Golan, Talia ; Domb, Abraham J. ; Yavin, Eylon ; Giladi, Hilla ; Rivkin, Ludmila ; Simerzin, Alina ; Eliakim, Rami ; Khalaileh, Abed ; Hubert, Ayala ; Lahav, Maor ; Kopelman, Yael ; Goldin, Eran ; Dancour, Alan ; Hants, Yael ; Arbel-Alon, Sagit ; Abramovitch, Rinat ; Shemi, Amotz ; Galun, Eithan

Pancreatic ductal adenocarcinoma (PDA) represents an unmet therapeutic challenge. PDA is addicted to the activity of the mutated KRAS oncogene which is considered so far an undruggable therapeutic target. We propose an approach to target KRAS effectively in patients using RNA interference. To meet this challenge, we have developed a local prolonged siRNA delivery system (Local Drug EluteR, LODER) shedding siRNA against the mutated KRAS (siG12D LODER). The siG12D LODER was assessed for its [...]

Cet article passe en revue les perspectives offertes par le ciblage du gène MET pour le traitement des patients atteints d'un cancer du poumon non à petites cellules

Targeting the MET gene for the treatment of non-small-cell lung cancer

Gelsomino, F. ; Facchinetti, F. ; Haspinger, E. R. ; Garassino, M. C. ; Trusolino, L. ; De Braud, F. ; Tiseo, M.

Recently, a better understanding of the specific mechanisms of oncogene addiction has led to the development of antitumor strategies aimed at blocking these abnormalities in different malignancies, including lung cancer. These abnormalities trigger constitutive activation of tyrosine kinase receptors (RTKs) involved in fundamental cell mechanisms such as proliferation, survival, differentiation and migration, and consequently the aberrant signaling of RTKs leads to cancer growth and survival. [...]

Menée in vitro, cette étude met en évidence des mécanismes par lesquels des mutations du gène DDR2 et la perte du gène NF1 favorisent une résistance au dasatinib dans le traitement des patients atteints d'un cancer du poumon non à petites cellules

Acquired resistance to dasatinib in lung cancer cell lines conferred by DDR2 gatekeeper mutation and NF1 loss

Beauchamp, Ellen M. ; Woods, Brittany A. ; Dulak, Austin M. ; Tan, Li ; Xu, Chunxiao ; Gray, Nathanael S. ; Bass, Adam J. ; Wong, Kwok-Kin ; Meyerson, Matthew ; Hammerman, Peter S.

The treatment of non-small cell lung cancer has evolved dramatically over the past decade with the adoption of widespread use of effective targeted therapies in patients with distinct molecular alterations. In lung squamous cell carcinoma (lung SqCC) recent studies have suggested that DDR2 mutations are a biomarker for therapeutic response to dasatinib and clinical trials are underway testing this hypothesis. While targeted therapeutics are typically quite effective as initial therapy for [...]

Menée sur des échantillons tumoraux et des lignées cellulaires, cette étude française met en évidence des mécanismes par lesquels l'interleukine 17A favorise la prolifération des cellules tumorales et la résistance aux chimiothérapies dans certaines formes de cancer du sein

IL-17A is produced by breast cancer TILs and promotes chemoresistance and proliferation through ERK1/2

Cochaud, Stéphanie ; Giustiniani, Jérôme ; Thomas, Clémence ; Laprevotte, Emilie ; Garbar, Christian ; Savoye, Aude-Marie ; Curé, Hervé ; Mascaux, Corinne ; Alberici, Gilles ; Bonnefoy, Nathalie ; Eliaou, Jean-François ; Bensussan, Armand ; Bastid, Jeremy

The proinflammatory cytokine Interleukin 17A (hereafter named IL–17A) or IL-17A producing cells are elevated in breast tumors environment and correlate with poor prognosis. Increased IL-17A is associated with ER(−) or triple negative tumors and reduced Disease Free Survival. However, the pathophysiological role of IL-17A in breast cancer remains unclear although several studies suggested its involvement in cancer cell dissemination. Here we demonstrated that a subset of breast tumors is [...]

A partir d'une analyse à l'échelle d'une seule cellule d'échantillons tumoraux prélevés sur des patients atteints d'un glioblastome traité à l'aide d'inhibiteurs de l'activité tyrosine kinase d'EGFR, cette étude met en évidence le rôle joué par des fragments d'ADN extrachromosomique dans l'apparition d'une résistance thérapeutique

Targeted Therapy Resistance Mediated by Dynamic Regulation of Extrachromosomal Mutant EGFR DNA

Nathanson, David A. ; Gini, Beatrice ; Mottahedeh, Jack ; Visnyei, Koppany ; Koga, Tomoyuki ; Gomez, German ; Eskin, Ascia ; Hwang, Kiwook ; Wang, Jun ; Masui, Kenta ; Paucar, Andres ; Yang, Huijin ; Ohashi, Minori ; Zhu, Shaojun ; Wykosky, Jill ; Reed, Rachel ; Nelson, Stanley F. ; Cloughesy, Timothy F. ; James, C. David ; Rao, P. Nagesh ; Kornblum, Harley I. ; Heath, James R. ; Cavenee, Webster K. ; Furnari, Frank B. ; Mischel, Paul S.

Intratumoral heterogeneity contributes to cancer drug resistance, but the underlying mechanisms are not understood. Single cell analyses of patient-derived models and clinical samples from glioblastoma patients treated with EGFR tyrosine kinase inhibitors (TKIs) demonstrate that tumor cells reversibly up-regulate or suppress mutant EGFR expression, conferring distinct cellular phenotypes to reach an optimal equilibrium for growth. Resistance to EGFR TKIs is shown to occur by elimination of [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude évalue l'activité antitumorale d'un composé appelé JQ1, un inhibiteur des bromodomaines de BET, pour le traitement d'un médulloblastome avec amplification du gène MYC

BET-bromodomain inhibition of MYC-amplified Medulloblastoma

Bandopadhayay, Pratiti ; Bergthold, Guillaume ; Nguyen, Brian ; Schubert, Simone ; Gholamin, Sharareh ; Tang, Yujie ; Bolin, Sara ; Schumacher, Steven E ; Zeid, Rhamy ; Masoud, Sabran ; Yu, Furong ; Vue, Nujsaubnusi ; Gibson, William J ; Paolella, Brenton R ; Mitra, Siddhartha S ; Cheshier, Samuel ; Qi, Jun ; Liu, Kun-Wei ; Wechsler-Reya, Robert J ; Weiss, William A. ; Swartling, Fredrik J ; Kieran, Mark W ; Bradner, James E. ; Beroukhim, Rameen ; Cho, Yoon-Jae

Purpose:MYC-amplified medulloblastomas are highly lethal tumors. BET bromodomain inhibition has recently been shown to suppress MYC-associated transcriptional activity in other cancers. The compound JQ1 inhibits BET bromodomain-containing proteins, including BRD4. Here we investigate BET bromodomain targeting for the treatment of MYC-amplified medulloblastoma. Experimental Design:We evaluated the effects of genetic and pharmacological inhibition of BET bromodomains on proliferation, cell cycle, [...]

Cet article passe en revue les travaux récents sur le diagnostic et la prise en charge des complications cutanées associées aux traitements anti-angiogéniques, notamment le bévacizumab, le sorafénib et le sunitinib

Cutaneous manifestations of anti-angiogenic therapy in oncology: Review with focus on VEGF inhibitors

Ishak, Rim S. ; Aad, Simon Abi ; Kyei, Angela ; Farhat, Fadi S.

The role of the VEGF signaling pathway in angiogenesis has been extensively investigated, and many new targeted anti-angiogenic drugs have evolved from this knowledge. The recent approval and introduction of these anti-neoplastic drugs has revolutionized the treatment of many types of cancers, but has also revealed numerous toxicities to the skin and its adnexae. Since these cutaneous side effects may have a significant impact on the physical, emotional and psychosocial health of patients, it [...]

Mené sur 519 patients atteints d'une leucémie myéloïde chronique en phase chronique, cet essai de phase III (DASISION) compare, du point de vue des réponses moléculaires et cytogénétiques précoces, l'efficacité du dasatinib et de l'imatinib (durée de suivi : 3 ans)

Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION)

Jabbour, Elias ; Kantarjian, Hagop M. ; Saglio, Giuseppe ; Steegmann, Juan Luis ; Shah, Neil P. ; Boqué, Concepción ; Chuah, Charles ; Pavlovsky, Carolina ; Mayer, Jiri ; Cortes, Jorge ; Baccarani, Michele ; Kim, Dong-Wook ; Bradley-Garelik, M. Brigid ; Mohamed, Hesham ; Wildgust, Mark ; Hochhaus, Andreas

This analysis explores the impact of early cytogenetic and molecular responses on the outcomes of patients with chronic myeloid leukemia in chronic phase (CML-CP) in the phase 3 DASISION trial with a minimum follow-up of 3 years. Patients with newly diagnosed CML-CP were randomized to receive 100 mg dasatinib (n = 259) or 400 mg imatinib (n = 260) once daily. The retrospective landmark analysis included patients evaluable at the relevant time point (3, 6, or 12 months). Median time to complete [...]

Mené sur 142 patientes atteintes d'un cancer de l'ovaire résistant aux sels de platine, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité du phénoxodiol en complément d'un traitement à l'aide de carboplatine AUC2

Weekly AUC2 carboplatin in acquired platinum-resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity: the phase III OVATURE multicenter randomized study

Fotopoulou, C. ; Vergote, I. ; Mainwaring, P. ; Bidzinski, M. ; Vermorken, J. B. ; Ghamande, S. A. ; Harnett, P. ; Del Prete, S. A. ; Green, J. A. ; Spaczynski, M. ; Blagden, S. ; Gore, M. ; Ledermann, J. ; Kaye, S. ; Gabra, H.

Background Platinum-resistant ovarian cancer (PROC) constitutes a therapeutic dilemma with limited efficacy from traditional cytotoxic agents. Based on prior data suggesting that scheduling alterations of platinum would increase activity, the aim of the present study was to assess the potential therapeutic benefit of phenoxodiol (PXD), a novel biomodulator shown to have chemoresistance reversing potential, when combined with weekly AUC2-carboplatin in PROC patients. Patients and methods A [...]

Mené sur 353 patients atteints d'un cancer du poumon et recevant un traitement adjuvant FOLFOX, cet essai de phase III évalue l'efficacité d'injections de calcium/magnésium pour prévenir les neurotoxicités induites par l'oxaliplatine

Phase III Randomized, Placebo-Controlled, Double-Blind Study of Intravenous Calcium and Magnesium to Prevent Oxaliplatin-Induced Sensory Neurotoxicity (N08CB/Alliance)

Loprinzi, Charles L. ; Qin, Rui ; Dakhil, Shaker R. ; Fehrenbacher, Louis ; Flynn, Kathleen A. ; Atherton, Pamela ; Seisler, Drew ; Qamar, Rubina ; Lewis, Grant C. ; Grothey, Axel

Purpose Cumulative neurotoxicity is a prominent toxicity of oxaliplatin-based therapy. Intravenous calcium and magnesium have been extensively used to reduce oxaliplatin-induced neurotoxicity. This trial was designed to definitively test whether calcium/magnesium decreases oxaliplatin-related neurotoxicity. Patients and Methods In all, 353 patients with colon cancer undergoing adjuvant therapy with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) were randomly assigned to intravenous [...]

Mené sur 791 patients atteints d'un carcinome rénal métastatique, cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression, et la toxicité de deux combinaisons (temsirolimus-bévacizumab et interféron alpha-bévacizumab) en traitement de première ligne

Randomized Phase III Trial of Temsirolimus and Bevacizumab Versus Interferon Alfa and Bevacizumab in Metastatic Renal Cell Carcinoma: INTORACT Trial

Rini, Brian I. ; Bellmunt, Joaquim ; Clancy, Jill ; Wang, Kongming ; Niethammer, Andreas G. ; Hariharan, Subramanian ; Escudier, Bernard

Purpose To prospectively determine the efficacy of combination therapy with temsirolimus plus bevacizumab versus interferon alfa (IFN) plus bevacizumab in metastatic renal cell carcinoma (mRCC). Patients and Methods In a randomized, open-label, multicenter, phase III study, patients with previously untreated predominantly clear-cell mRCC were randomly assigned, stratified by prior nephrectomy and Memorial Sloan-Kettering Cancer Center prognostic group, to receive the combination of either [...]

Mené sur 512 patients atteints d'un carcinome rénal métastatique ayant progressé après un traitement au sunitinib, cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression, et la toxicité du temsirolimus et du sorafénib en traitement de seconde ligne

Randomized Phase III Trial of Temsirolimus Versus Sorafenib As Second-Line Therapy After Sunitinib in Patients With Metastatic Renal Cell Carcinoma

Hutson, Thomas E. ; Escudier, Bernard ; Esteban, Emilio ; Bjarnason, Georg A. ; Lim, Ho Yeong ; Pittman, Kenneth B. ; Senico, Peggy ; Niethammer, Andreas ; Lu, Dongrui Ray ; Hariharan, Subramanian ; Motzer, Robert J.

Purpose This international phase III trial (Investigating Torisel As Second-Line Therapy [INTORSECT]) compared the efficacy of temsirolimus (mammalian target of rapamycin inhibitor) and sorafenib (vascular endothelial growth factor receptor [VEGFR] tyrosine kinase inhibitor) as second-line therapy in patients with metastatic renal cell carcinoma (mRCC) after disease progression on sunitinib. Patients and Methods In total, 512 patients were randomly assigned 1:1 to receive intravenous [...]

Mené sur 736 patientes atteintes d'un cancer du sein récividant ou métastatique (âge médian : 61 ans), cet essai de phase III (CONFIRM) compare, du point de vue de la survie globale, l'efficacité de deux dosages de fulvestrant (500 mg et 250 mg)

Final Overall Survival: Fulvestrant 500mg vs 250mg in the Randomized CONFIRM Trial

Leo, Angelo Di ; Jerusalem, Guy ; Petruzelka, Lubos ; Torres, Roberto ; Bondarenko, Igor N. ; Khasanov, Rustem ; Verhoeven, Didier ; Pedrini, José L. ; Smirnova, Iya ; Lichinitser, Mikhail R. ; Pendergrass, Kelly ; Malorni, Luca ; Garnett, Sally ; Rukazenkov, Yuri ; Martin, Miguel

Background At the time of the initial analysis of overall survival (OS) for the Comparison of Faslodex in Recurrent or Metastatic Breast Cancer (CONFIRM) randomized, double-blind, phase III trial, approximately 50% of patients had died. A final analysis of OS was subsequently planned for when 75% of patients had died. Methods Patients were randomly assigned 1:1 to fulvestrant 500 mg administered as two 5-mL intramuscular injections on days 0, 14, and 28 and every 28 (±3) days thereafter or [...]

Menée in vitro et à l'aide de xénogreffes de cancer du pancréas sur un modèle murin, cette étude montre qu'un vaccin oncolytique (GLV-1h151) et une radiothérapie peuvent avoir un effet synergique contre les cellules tumorales

Oncolytic vaccinia virus in combination with radiation shows synergistic antitumor efficacy in pancreatic cancer

Dai, M. H. ; Liu, S. L. ; Chen, N. G. ; Zhang, T. P. ; You, L. ; Zhang, F. Q. ; Chou, T. C. ; Szalay, A. A. ; Fong, Y. ; Zhao, Y. P.

Combining oncolytic viruses with conventional therapy such as radiation is an innovative option for pancreatic cancer. We demonstrated that combination of GLV-1h151 and radiation yielded a synergistic cytotoxic effect, with the greatest effect achieved in the AsPC-1cell line. Combination treatment significantly increased apoptosis compared with either single treatment or the control group. In mice bearing human pancreatic tumor xenografts, combination treatment resulted in significantly [...]

Mené sur 18 patients atteints d'un adénocarcinome rectal de stade II ou III (durée médiane de suivi : 34 mois), cet essai de phase I évalue l'efficacité, du point de vue de la survie sans maladie à 3 ans, et la dose maximale tolérée de la capécitabine, du bevacizumab et de l'erlotinib en combinaison avec une radiothérapie concomitante pré-opératoire

Preoperative Radiation Therapy With Concurrent Capecitabine, Bevacizumab, and Erlotinib for Rectal Cancer: A Phase 1 Trial

Das, Prajnan ; Eng, Cathy ; Rodriguez-Bigas, Miguel A. ; Chang, George J. ; Skibber, John M. ; You, Y. Nancy ; Maru, Dipen M. ; Munsell, Mark F. ; Clemons, Marilyn V. ; Kopetz, Scott E. ; Garrett, Christopher R. ; Shureiqi, Imad ; Delclos, Marc E. ; Krishnan, Sunil ; Crane, Christopher H.

Purpose : The goal of this phase 1 trial was to determine the maximum tolerated dose (MTD) of concurrent capecitabine, bevacizumab, and erlotinib with preoperative radiation therapy for rectal cancer. Methods and Materials : Patients with clinical stage II to III rectal adenocarcinoma, within 12 cm from the anal verge, were treated in 4 escalating dose levels, using the continual reassessment method. Patients received preoperative radiation therapy with concurrent bevacizumab (5 mg/kg [...]

A partir d'un échantillon de 600 essais cliniques enregistrés, avec des résultats, dans la base ClinicalTrials.gov en mars 2012, cette étude évalue les différences entre ces résultats et ceux publiés dans les revues médicales

Timing and Completeness of Trial Results Posted at ClinicalTrials.gov and Published in Journals

Riveros, Carolina ; Dechartres, Agnes ; Perrodeau, Elodie ; Haneef, Romana ; Boutron, Isabelle ; Ravaud, Philippe

Background : The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration–approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. Methods and Findings : We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of [...]

Cette étude américaine analyse les défis posés par le respect des recommandations de FDA en matière d'évaluation de l'intensité de la douleur et de sa prise en charge dans les essais cliniques en cancérologie

Pain palliation measurement in cancer clinical trials: The US Food and Drug Administration perspective

Basch, Ethan ; Trentacosti, Ann Marie ; Burke, Laurie B. ; Kwitkowski, Virginia ; Kane, Robert C. ; Autio, Karen A. ; Papadopoulos, Elektra ; Stansbury, James P. ; Kluetz, Paul G. ; Smith, Harry ; Justice, Robert ; Pazdur, Richard

BACKGROUND : Pain palliation resulting from antitumor therapy provides direct evidence of treatment benefit when combined with evidence of antitumor activity. The US Food and Drug Administration (FDA) previously issued guidance regarding the use of patient-reported outcome (PRO) measures to support labeling claims. The purpose of this article is to identify common challenges and key design strategies when measuring pain palliation in antitumor therapy clinical trials that are consistent with [...]